L4 - Glucose and Diabetes

Question 1

What are the acinar cells in the pancreas?

Answer 1

Acinar cells are found in the exocrine portion of the pancreas.
They secrete digestive enzymes (e.g., amylase, lipase, trypsinogen) into the pancreatic duct, which leads to the small intestine for digestion of carbohydrates, fats, and proteins.

Question 2

What are the Islets of Langerhans?

Answer 2

The Islets of Langerhans are clusters of endocrine cells located in the pancreas.
They are responsible for producing hormones that regulate glucose metabolism, including:
Alpha cells: Secrete glucagon, which increases blood glucose levels.
Beta cells: Secrete insulin, which decreases blood glucose levels.
Delta cells: Secrete somatostatin, which inhibits insulin and glucagon release.
PP cells: Secrete pancreatic polypeptide, which regulates pancreatic secretion and appetite.

Question 3

What are the functions of the cells in the Islets of Langerhans?
A:

Answer 3

β cells: Secrete insulin, which lowers blood glucose by promoting glucose uptake in cells.
α cells: Secrete glucagon, which raises blood glucose by stimulating the liver to release glucose.
δ cells: Secrete somatostatin, which inhibits insulin and glucagon release and regulates the digestive process.
PP cells: Secrete pancreatic polypeptide, which increases gastric enzyme secretion and decreases gastric motility

Question 4

What is the role of acinar cells in the pancreas?

Answer 4

Acinar cells are part of the exocrine pancreas.
They produce digestive enzymes (e.g., amylase, lipase, trypsinogen) that are secreted into the pancreatic duct, which carries them to the small intestine for digestion of nutrients.

Question 5

How are the Islets of Langerhans and acinar cells functionally different in the pancreas?

Answer 5

Islets of Langerhans are part of the endocrine pancreas and secrete hormones like insulin, glucagon, and somatostatin into the bloodstream for glucose regulation.
Acinar cells are part of the exocrine pancreas and secrete digestive enzymes into ducts leading to the small intestine for nutrient digestion.

Question 6

What is the role of insulin in glucose homeostasis?

Answer 6

Insulin lowers blood glucose levels by promoting:
Fat synthesis (lipogenesis)
Protein synthesis
Glycogen synthesis (glycogenesis)
Glucose uptake into cells, especially in muscle and adipose tissue.

Question 7

What is the role of glucagon in glucose homeostasis?

Answer 7

Glucagon raises blood glucose levels by stimulating:
Gluconeogenesis (glucose production from non-carbohydrate sources) in the liver
Glycogen breakdown (glycogenolysis) to release glucose
Fatty acid catabolism (lipolysis) for energy production.

Question 8

How do insulin and glucagon work together in maintaining glucose homeostasis?

Answer 8

Insulin and glucagon act in opposition to maintain blood glucose levels:
Insulin promotes the storage of glucose (as glycogen), fat, and protein when glucose levels are high.
Glucagon promotes the release of glucose by stimulating gluconeogenesis, glycogen breakdown, and fat catabolism when glucose levels are low.

Question 9

What are the blood glucose levels for hypoglycaemia, normoglycaemia, and hyperglycaemia?

Answer 9

Hypoglycaemia: < 3.5 mmol/L
Normoglycaemia: 3.5 - 7.5 mmol/L
Hyperglycaemia: > 7.5 mmol/L

Question 10

How does the body respond to hypoglycaemia?

Answer 10

Hypoglycaemia (< 3.5 mmol/L) triggers:
Increased glucagon release from α cells
Increased glycogenolysis (glycogen breakdown)
Increased gluconeogenesis (glucose production from non-carbohydrate sources)
Increased proteolysis (protein breakdown for glucose synthesis)
Decreased glucose uptake into cells.

Question 11

How does the body respond to hyperglycaemia (post-prandial)?

Answer 11

Hyperglycaemia (> 7.5 mmol/L) triggers:
Increased insulin release from β cells
Increased glycolysis (glucose breakdown for energy)
Increased glycogenesis (glycogen formation)
Increased glucose uptake into cells for energy storage.

Question 12

How does the body respond to starvation in terms of glucose homeostasis?

Answer 12

During starvation:
Increased glucagon release from α cells
Increased glycogenolysis and gluconeogenesis to maintain blood glucose levels
Decreased glucose uptake into cells
Increased proteolysis to generate amino acids for gluconeogenesis.

Question 13

What are the key steps in glucagon release from pancreatic α cells?

Answer 13

ATP levels increase (due to low glucose levels)
This causes K+ channels (KATP) to close, leading to membrane depolarisation
Depolarisation activates voltage-gated Ca2+ channels, allowing Ca2+ to enter the cell
The increase in Ca2+ triggers the release of glucagon from α cells.

Question 14

What is the role of GLUT-1 in glucagon release?

Answer 14

GLUT-1 facilitates glucose uptake into pancreatic cells.
Low glucose levels lead to reduced GLUT-1 activity, triggering the signalling cascade for glucagon release.

Question 15

How does membrane depolarisation lead to glucagon release?

Answer 15

Depolarisation occurs when KATP channels close due to low ATP levels, resulting in reduced K+ efflux.
This depolarisation opens voltage-gated Ca2+ channels, allowing Ca2+ influx, which initiates the release of glucagon from α cells.

Question 16

What are the key steps in glucagon signalling in hepatocytes, adipocytes, and skeletal muscle?

Answer 16

Glucagon binds to the glucagon receptor on the target cell.
This activates Gs (G-protein), which stimulates adenylyl cyclase (AC).
AC increases cAMP levels, which activates protein kinase A (PKA).
In hepatocytes, this leads to increased gluconeogenesis and glycogenolysis, and decreased glycogenesis.
In adipocytes, glucagon stimulates lipolysis, increasing fatty acid release.
In skeletal muscle, glucagon has minimal direct effects but can influence metabolism via systemic effects.

Question 17

What is the role of cAMP and PKA in glucagon signalling?

Answer 17

cAMP is produced in response to glucagon receptor activation.
cAMP activates PKA (protein kinase A), which then phosphorylates various enzymes involved in glycogen breakdown (glycogenolysis), glucose production (gluconeogenesis), and inhibition of glycogen synthesis (glycogenesis).

Question 18

How does glucagon affect glycogen metabolism?
A:

Answer 18

Glucagon activates glycogenolysis (breakdown of glycogen to glucose) by increasing cAMP and PKA activity.
Glycogen synthesis (glycogenesis) is inhibited by glucagon.
Gluconeogenesis is stimulated to produce more glucose from non-carbohydrate sources.

Question 19

What are the clinical uses of glucagon?

Answer 19

Glucagon is used for emergency treatment of hypoglycaemia (low blood sugar) with reduced consciousness.
It can be administered via subcutaneous, intramuscular injection, or intravenous infusion.

Question 20

What are the adverse effects of glucagon?

Answer 20

The common adverse effects include nausea and vomiting.

Question 21

What is the mechanism of insulin release from pancreatic β cells?
A:

Answer 21

Glucose enters β cells through GLUT-2 transporters.
ATP production from glucose metabolism causes the K+ATP channels to close.
This leads to membrane depolarisation, which opens voltage-gated Ca2+ channels.
The influx of Ca2+ triggers the release of insulin.

Question 22

How do sulfonylurea drugs affect insulin release?
A:

Answer 22

Sulfonylurea drugs bind to the sulfonylurea receptor on K+ATP channels, causing them to close.
This induces membrane depolarisation, leading to Ca2+ influx and subsequent insulin release.

Question 23

What are the actions of insulin on glucose metabolism?

Answer 23

Increase in glycogenesis (glycogen synthesis).
Increase in glycolysis (glucose breakdown for energy).
Decrease in gluconeogenesis (glucose production from non-carbohydrate sources).
Increase in glucose uptake by cells.

Question 24

How does insulin affect lipid metabolism?

Answer 24

Increase in lipogenesis (fatty acid and triglyceride synthesis).
Decrease in lipolysis (fat breakdown).

Question 25

How does insulin influence protein metabolism?

Answer 25

Increase in protein synthesis (building proteins from amino acids).

Question 26

What is the role of insulin in skeletal muscle and adipose tissue glucose homeostasis?

Answer 26

Insulin binds to the insulin receptor, triggering a cascade that activates IRS (Insulin Receptor Substrate) and PI3K (Phosphoinositide 3-Kinase). This activation leads to the phosphorylation of Akt, which facilitates the translocation of GLUT-4 (glucose transporter) vesicles to the cell surface, increasing glucose uptake.

Question 27

What is the function of GLUT-4 in skeletal muscle and adipose tissue?

Answer 27

GLUT-4 transports glucose into skeletal muscle and adipose tissue cells in response to insulin stimulation.

Question 28

What signalling pathway is involved in insulin-mediated glucose uptake in muscle and adipose tissue?

Answer 28

Insulin binds to the insulin receptor, activating the IRS/PI3K/Akt signalling pathway, leading to GLUT-4 translocation and increased glucose uptake.

Question 29

How does insulin regulate glucose homeostasis in the liver?

Answer 29

Insulin binds to its receptor on hepatocytes, activating the IRS/PI3K/Akt pathway. This pathway reduces glycogenolysis (breakdown of glycogen) and gluconeogenesis (glucose production), promoting glucose uptake via GLUT-2 and conversion to glucose-6-phosphate by glucokinase.

Question 30

What is the role of GLUT-2 in hepatocytes during insulin-mediated glucose uptake?

Answer 30

GLUT-2 facilitates the uptake of glucose into hepatocytes in response to insulin, enabling the conversion of glucose to glucose-6-phosphate.

Question 31

How does insulin affect glycogenolysis and gluconeogenesis in the liver?

Answer 31

Insulin inhibits glycogenolysis (breakdown of glycogen) and gluconeogenesis (production of glucose) in the liver, promoting glucose storage and decreased glucose output.

Question 32

What is the role of glucokinase in glucose metabolism in the liver?

Answer 32

Glucokinase in hepatocytes phosphorylates glucose to form glucose-6-phosphate, which can be used in glycogen synthesis or other metabolic pathways.

Question 33

What are the main types of diabetes?

Answer 33

Type 1: Autoimmune disease, insulin deficient, often young onset, insulin dependent. Type 2: Metabolic disorder, insulin resistance with some insulin deficiency, typically older onset, not enough insulin production. Gestational diabetes: Occurs in the 2nd/3rd trimester, risk to both parent and child.

Question 34

What is the main cause of Type 1 diabetes?

Answer 34

Type 1 diabetes is an autoimmune disorder that leads to the destruction of insulin-producing beta cells in the pancreas, causing insulin deficiency.

Question 35

How does Type 2 diabetes differ from Type 1 diabetes in terms of insulin production?

Answer 35

In Type 1 diabetes, there is an insulin deficiency due to beta-cell destruction. In Type 2 diabetes, there is insulin resistance and some insulin deficiency, but the pancreas may still produce insulin.

Question 36

What are the risks associated with gestational diabetes?

Answer 36

Gestational diabetes poses risks to both the parent and the child, including potential complications during pregnancy and delivery.

Question 37

What is Type 2 Diabetes Mellitus (T2DM)?

Answer 37

T2DM is a metabolic disorder characterised by insulin resistance and, eventually, insulin deficiency. It usually occurs in older adults but can affect younger individuals, particularly with obesity or sedentary lifestyle.

Question 38

What is the main pathophysiology behind Type 2 Diabetes?

Answer 38

In T2DM, there is insulin resistance, where the body's cells (particularly muscle and adipose tissue) do not respond effectively to insulin. Over time, this leads to increased blood glucose levels and eventual insulin secretion deficiency.

Question 39

What are the risk factors for developing Type 2 Diabetes?

Answer 39

Obesity, particularly abdominal fat. Physical inactivity. Family history of diabetes. Age (greater risk in individuals over 45). Poor diet, especially diets high in sugars and fats. Hypertension and dyslipidaemia.

Question 40

What are the main clinical manifestations of Type 2 Diabetes?

Answer 40

Increased thirst (polydipsia). Increased urination (polyuria). Fatigue. Blurred vision. Slow healing wounds. Frequent infections.

Question 41

How is Type 2 Diabetes diagnosed? A:

Answer 41

Through blood tests showing: Fasting plasma glucose (FPG) ≥ 7.0 mmol/L. Oral glucose tolerance test (OGTT): 2-hour plasma glucose ≥ 11.1 mmol/L. HbA1c ≥ 6.5% (48 mmol/mol).

Question 42

What is the role of insulin resistance in the development of Type 2 Diabetes?

Answer 42

Insulin resistance reduces the effectiveness of insulin in muscle, adipose tissue, and liver, leading to impaired glucose uptake, increased glucose production by the liver, and ultimately hyperglycaemia.

Question 43

What are the treatment options for Type 2 Diabetes?

Answer 43

Lifestyle modifications: Weight loss, improved diet, and increased physical activity. Medications: Metformin (first-line treatment). Sulfonylureas, DPP-4 inhibitors, GLP-1 agonists, and SGLT2 inhibitors. Insulin therapy may be required in advanced stages.

Question 44

What are the main metabolic defects in Type 2 Diabetes Mellitus (T2DM)? A:

Answer 44

Obesity: Excess fat leads to increased free fatty acids (FFAs) and adipokines, which contribute to insulin resistance and inflammation. Insulin resistance: Cells in muscle, adipose tissue, and the liver do not respond properly to insulin, impairing glucose uptake and causing elevated blood glucose levels. Increased FFAs: Elevated free fatty acids lead to lipid accumulation in non-adipose tissues, further worsening insulin resistance. Adipokines and inflammation: Imbalance in adipokines (hormones secreted by fat cells) promotes inflammatory pathways and insulin resistance.

Question 45

How does obesity contribute to insulin resistance in Type 2 Diabetes?

Answer 45

Obesity, particularly visceral fat, increases the release of free fatty acids (FFAs) and adipokines. These molecules promote inflammation and disrupt the insulin signalling pathway, leading to decreased insulin sensitivity and increased blood glucose levels.

Question 46

What role do free fatty acids (FFAs) play in insulin resistance in Type 2 Diabetes?

Answer 46

FFAs can accumulate in muscle and liver cells, leading to lipotoxicity. This inhibits insulin signalling pathways, contributing to insulin resistance and reduced glucose uptake by cells, which increases blood glucose levels.

Question 47

How do adipokines contribute to insulin resistance and inflammation in Type 2 Diabetes?

Answer 47

Adipokines are hormones secreted by adipose tissue. In obesity, an imbalance of these hormones (e.g., increased resistin and decreased adiponectin) promotes low-grade inflammation and disrupts insulin signalling, further exacerbating insulin resistance and contributing to the development of T2DM.

Question 48

What is the role of inflammation in the pathophysiology of Type 2 Diabetes?

Answer 48

Chronic low-grade inflammation in adipose tissue, driven by increased FFAs and altered adipokine secretion, activates inflammatory pathways that interfere with insulin signalling and increase insulin resistance, contributing to the progression of Type 2 Diabetes.

Question 49

What are the main treatment strategies for Type 2 Diabetes Mellitus (T2DM)?

Answer 49

Lifestyle modifications: Diet: Emphasis on a balanced, low-glycemic, and calorie-controlled diet. Exercise: Regular physical activity to improve insulin sensitivity and reduce blood glucose levels. Weight loss: Achieving and maintaining a healthy weight can help reverse insulin resistance. Pharmacological treatment: Metformin: First-line drug that improves insulin sensitivity and reduces hepatic glucose production. Sulfonylureas: Stimulate insulin secretion from the pancreas. GLP-1 receptor agonists: Enhance insulin release, inhibit glucagon release, and slow gastric emptying. SGLT2 inhibitors: Promote renal glucose excretion. Thiazolidinediones: Improve insulin sensitivity in muscle and adipose tissue.

Question 50

How does Metformin help in the treatment of Type 2 Diabetes Mellitus (T2DM)?

Answer 50

Metformin works by reducing hepatic glucose production and improving insulin sensitivity in peripheral tissues (e.g., muscle and adipose). This leads to a decrease in blood glucose levels, particularly after meals, and helps reduce insulin resistance.

Question 51

What is the role of Sulfonylureas in treating Type 2 Diabetes?

Answer 51

Sulfonylureas stimulate insulin secretion from the pancreas by binding to the sulfonylurea receptor on β-cells, which leads to membrane depolarisation and calcium influx, triggering insulin release. These drugs are used when oral glucose-lowering agents like Metformin are insufficient.

Question 52

How do GLP-1 receptor agonists work in Type 2 Diabetes treatment?

Answer 52

GLP-1 receptor agonists mimic the action of the glucagon-like peptide 1 (GLP-1) hormone, which enhances insulin secretion in response to meals, suppresses glucagon release, and slows gastric emptying. This results in lower blood glucose levels and reduced appetite.

Question 53

What is the mechanism of action of SGLT2 inhibitors in Type 2 Diabetes?

Answer 53

SGLT2 inhibitors block the Sodium-Glucose Cotransporter 2 (SGLT2) in the kidneys, which reduces glucose reabsorption and increases renal glucose excretion. This helps lower blood glucose levels and can lead to weight loss and blood pressure reduction.

Question 54

What role do Thiazolidinediones (e.g., pioglitazone) play in treating Type 2 Diabetes? A:

Answer 54

Thiazolidinediones increase insulin sensitivity in muscle and adipose tissue by activating the PPAR-γ receptor, which enhances the uptake of glucose and fatty acids. These drugs help improve insulin action and reduce blood glucose levels over time.

Question 55

What are the key goals of lifestyle interventions in managing Type 2 Diabetes? A:

Answer 55

Weight loss: Helps reduce insulin resistance and improve glucose control. Dietary modifications: Focus on a low-glycemic and calorie-controlled diet to manage blood glucose levels. Exercise: Regular physical activity improves insulin sensitivity and helps maintain blood glucose control.

Question 56

What are the key points about Biguanides (Metformin) in the treatment of Type 2 Diabetes?

Answer 56

First-line treatment for Type 2 Diabetes. Half-life of 3 hours. Excreted in urine.

Question 57

What are the adverse effects of Metformin (Biguanides)?

Answer 57

Gastrointestinal disturbances (e.g., nausea, diarrhoea). Lactic acidosis (a rare but serious complication). Interference with Vitamin B12 absorption, potentially leading to deficiency.

Question 58

How does Metformin work to lower blood glucose in Type 2 Diabetes? A:

Answer 58

Metformin reduces hepatic glucose production and increases insulin sensitivity in peripheral tissues like muscle and adipose. This leads to better glucose uptake and lower blood glucose levels.

Question 59

What are the key points about Sulfonylureas in the treatment of Type 2 Diabetes?

Answer 59

Second-line treatment or used in dual therapy with Metformin. Mimic the action of ATP on KATP channels in pancreatic β-cells to increase insulin secretion.

Question 60

What are the adverse effects of Sulfonylureas?

Answer 60

Hypoglycaemia, especially when combined with certain drugs like NSAIDs. Polyphagia (increased hunger). Gastrointestinal upset (seen in 3% of patients).

Question 61

What are some examples of Sulfonylureas used in the treatment of Type 2 Diabetes?

Answer 61

Tolbutamide Glibenclamide

Question 62

What is the mechanism of action of Thiazolidinediones (glitazones) in the treatment of Type 2 Diabetes?

Answer 62

Activate PPARγ (Peroxisome Proliferator-Activated Receptor γ). Alter the function of adipocytes, hepatocytes, and myocytes. Increase GLUT4 expression for enhanced glucose uptake. Increase the uptake of free fatty acids (FFAs) and promote adipogenesis.

Question 63

What are the key points regarding the use of Thiazolidinediones (glitazones)? A:

Answer 63

Slow onset of action, typically taking 1-2 months for noticeable effects. Often combined with metformin to improve treatment outcomes. Altered glucose metabolism leading to improved insulin sensitivity.

Question 64

What is an example of a Thiazolidinedione (glitazone) used in the treatment of Type 2 Diabetes?

Answer 64

Rosiglitazone (often used as an example).

Question 65

What are the adverse effects associated with Thiazolidinediones (glitazones) like Pioglitazone? A:

Answer 65

Weight gain (stabilises after 6-12 months). Fluid retention (contraindicated in heart failure). Bone fractures. Oedema.

Question 66

What is an example of a Thiazolidinedione (glitazone) used in Type 2 Diabetes treatment?

Answer 66

Pioglitazone.

Question 67

How do Thiazolidinediones (glitazones), like Pioglitazone, affect glucose metabolism?

Answer 67

Activate PPARγ, increasing GLUT4 expression. Enhance glucose uptake in target tissues. Improve insulin sensitivity.

Question 68

What are the key effects of Incretins like GIP and GLP-1 on glucose metabolism?

Answer 68

Increase insulin secretion. Decrease glucagon secretion. Improve glycaemic control. Lower lipids.

Question 69

What is the role of Dipeptidyl peptidase-4 (DPP-4) in relation to Incretins?

Answer 69

DPP-4 inactivates GLP-1 and GIP, reducing their effects on insulin and glucagon regulation.

Question 70

How do GLP-1 mimetics influence pancreatic β cells?

Answer 70

GLP-1 mimetics activate Adenylyl Cyclase (Gs), leading to increased cAMP levels. This results in PKA activation, increased insulin secretion, and reduced apoptosis. Stimulates proliferation and differentiation of pancreatic β cells.

Question 71

What downstream signalling pathways are involved in the action of GLP-1 mimetics on pancreatic β cells? A:

Answer 71

EGFR activation. PI3K and C-SRC pathways. ERK pathway activation. Results in increased β cell proliferation and differentiation.

Question 72

How do GIP mimetics affect pancreatic β cells?

Answer 72

GIP mimetics activate Adenylyl Cyclase (Gs), increasing cAMP levels. This leads to PKA activation, increased insulin secretion, and reduced apoptosis in pancreatic β cells. Stimulates proliferation and differentiation of β cells.

Question 73

What are the key signalling pathways involved in GIP mimetics on pancreatic β cells?

Answer 73

MAPK and ERK pathway activation. Leads to decreased apoptosis and increased β cell proliferation and differentiation.

Question 74

What is Exenatide and its source?

Answer 74

Exenatide is an Incretin mimetic derived from Exendin-4, a peptide from the Gila monster.

Question 75

What are the adverse effects of Exenatide? A:

Answer 75

Weight loss (common effect). Pancreatitis (rare).

Question 75

What are the key benefits of Exenatide?

Answer 75

Causes significant weight loss. Administered via subcutaneous injection. Often used in combination drugs for diabetes management.

Question 76

What is Semaglutide and its type?

Answer 76

Semaglutide is a GLP-1 analogue used in the treatment of diabetes.

Question 77

How is Semaglutide administered?

Answer 77

It can be administered via weekly subcutaneous injection or as an oral preparation.

Question 78

What are the adverse effects of Semaglutide?

Answer 78

Alopecia (hair loss). Gastrointestinal disturbances. Diabetic retinopathy. Weight loss. Pancreatitis (rare). Angioedema. Hypoglycaemia (particularly with combination drugs).

Question 79

What is the function of DDP-4 inhibitors (Gliptins)?

Answer 79

DDP-4 inhibitors enhance the action of GIP and GLP-1 by preventing their breakdown, leading to: ↑ Insulin release. ↓ Glucagon secretion. Improved glycaemic control. Potentially ↓ lipids.

Question 80

What is an example of a Gliptin used in the treatment of diabetes?

Answer 80

n example of a Gliptin is Sitagliptin.

Question 81

How do DDP-4 inhibitors affect insulin and glucagon secretion?

Answer 81

DDP-4 inhibitors increase insulin secretion and decrease glucagon secretion, both of which help to lower blood glucose levels.

Question 82

What are the key points about Gliptins (DDP-4 inhibitors)?

Answer 82

No weight changes associated with Gliptins. Oral administration of Gliptins. Cannot be used with incretin mimetics. Renal excretion and CYP metabolism.

Question 83

What are the adverse effects of Gliptins (DDP-4 inhibitors)?

Answer 83

Gastrointestinal disturbances. Liver disease. Heart failure. Pancreatitis. Potential tumour-promoting effects.

Question 84

What is an example of a Gliptin (DDP-4 inhibitor)?

Answer 84

Sitagliptin is an example of a Gliptin.

Question 85

What is the mechanism of action of SGLT2 inhibitors?

Answer 85

SGLT2 inhibitors target the sodium-glucose co-transporter-2 (SGLT-2) in the proximal convoluted tubule of the kidney. They increase glucose excretion in urine.

Question 86

What are the key adverse effects of SGLT2 inhibitors? A:

Answer 86

Increased risk of urinary tract infections (UTI) and fungal infections. Hypotension and dehydration, especially when combined with diuretics. Ketoacidosis. Increased risk of necrotising fasciitis (Fournier's gangrene)

Question 87

What is an example of an SGLT2 inhibitor?

Answer 87

Empagliflozin is an example of an SGLT2 inhibitor.

Question 88

What is the mechanism of action of α-glucosidase inhibitors like Acarbose?

Answer 88

α-glucosidase inhibitors inhibit α-glucosidase, an enzyme responsible for breaking down oligosaccharides into monosaccharides (glucose). This reduces glucose absorption from the gastrointestinal tract, leading to lower postprandial glucose levels.

Question 89

What are the key adverse effects of Acarbose?

Answer 89

Gastrointestinal disturbances, including flatulence, diarrhoea, and abdominal pain. Hypoglycaemia when used with other anti-diabetic medications (treated with glucose, not sucrose).

Question 90

What is the mechanism of action of Acarbose as an α-glucosidase inhibitor? A:

Answer 90

Acarbose is a competitive inhibitor of α-glucosidase, an enzyme that breaks down oligosaccharides into monosaccharides (glucose). By inhibiting this enzyme, Acarbose slows glucose absorption from the gastrointestinal tract, reducing postprandial blood glucose levels.

Question 91

How does Acarbose affect glucose absorption?

Answer 91

Acarbose slows glucose absorption by inhibiting the breakdown of complex carbohydrates into simple sugars, leading to a reduction in postprandial glucose spikes.

Question 92

What are the pharmacokinetics of Acarbose?

Answer 92

<2% of Acarbose enters the systemic circulation. It acts locally in the intestine where it is metabolised by intestinal flora and digestive enzymes. Excretion occurs through kidneys and in faeces.

Question 93

What are the adverse effects associated with Acarbose?

Answer 93

Flatulence Loose stools and diarrhoea Abdominal pain and bloating

Question 94

What is Type 1 Diabetes Mellitus (T1DM)?

Answer 94

Autoimmune condition where the body's immune system attacks and destroys pancreatic β-cells, which are responsible for producing insulin. Leads to insulin deficiency, resulting in high blood glucose levels.

Question 95

What are the types of insulin used in diabetes management?

Answer 95

Short-acting insulin Rapid-acting insulin Intermediate-acting insulin Long-acting insulin Premixed insulin

Question 96

What is short-acting insulin?

Answer 96

Onset: 30-60 minutes Peak: 2-3 hours Duration: 6-8 hours Used for mealtime coverage to control postprandial blood glucose levels. Example: Regular insulin.

Question 97

What is rapid-acting insulin?

Answer 97

Onset: 10-30 minutes Peak: 1-2 hours Duration: 3-5 hours Designed for fast action to manage blood glucose after meals. Example: Insulin lispro, Insulin aspart, Insulin glulisine.

Question 98

What is intermediate-acting insulin?

Answer 98

Onset: 1-2 hours Peak: 4-12 hours Duration: 12-18 hours Often used to provide basal insulin coverage between meals and overnight. Example: NPH insulin.

Question 99

What is long-acting insulin?

Answer 99

Onset: 1-2 hours Peak: No pronounced peak Duration: Up to 24 hours Provides 24-hour basal insulin to maintain steady glucose levels. Example: Insulin glargine, Insulin detemir.

Question 100

What is premixed insulin?

Answer 100

A combination of short-acting and intermediate-acting insulins. Onset: 30 minutes Peak: Varies depending on the mixture Duration: 10-16 hours Used for convenience in patients who require both prandial and basal insulin. Example: 70/30 insulin mix (70% NPH, 30% regular insulin).

Question 101

What is the preparation and action timeline for short-acting insulin (Crystalline zinc insulin)? A:

Answer 101

Preparation: Crystalline zinc insulin Onset: 0.5-1.0 hours Peak: 2-3 hours Duration: 4-6 hours

Question 102

How is short-acting insulin typically administered?

Answer 102

Subcutaneous: Administered 30-45 minutes before a meal Emergencies: Can be given intramuscularly or intravenously

Question 103

How is Lispro insulin different from regular insulin in terms of its amino acid modifications?

Answer 103

Lispro insulin: B28 proline replaced with lysine, and B29 lysine replaced with proline.

Question 104

What are the delivery methods for Lispro insulin?

Answer 104

Subcutaneous: Administered immediately before a meal Emergencies: Can be given intramuscularly or intravenously

Question 105

How is Aspart insulin different from regular insulin in terms of its amino acid modification?

Answer 105

Aspart insulin: B28 proline replaced with aspartic acid.

Question 106

What is the effect of protamine on insulin?

Answer 106

Protamine complexes with insulin to delay absorption, resulting in a longer duration of action.

Question 107

What is the delivery method for insulin that is complexed with protamine?

Answer 107

Subcutaneous administration, typically once or twice per day.

Question 108

How is glargine insulin modified at the molecular level?

Answer 108

Glargine insulin contains 2x Arginine and 1x Glycine at the C-terminal of the B-chain.

Question 109

How does glargine insulin delay absorption?

Answer 109

Glargine insulin is formulated at a pH of 4, which stabilises the preparation and delays absorption.

Question 110

How does detemir insulin differ from glargine in terms of stabilisation? A:

Answer 110

Detemir insulin enhances albumin binding, which helps to stabilise the preparation and extend its duration of action.

Question 111

What is the delivery method for glargine and detemir insulin?

Answer 111

Subcutaneous administration, typically once or twice per day.

Question 112

What are the types of insulin and their general characteristics?

Answer 112

Short-acting (Crystalline Zinc Insulin) Onset: 0.5-1 hour Peak: 2-3 hours Duration: 4-6 hours Delivery: Subcutaneous, 30-45 minutes before meals Rapid-acting (Lispro & Aspart) Onset: 10-30 minutes Peak: 30-90 minutes Duration: 3-5 hours Delivery: Subcutaneous, immediately before meals Lispro: B28 proline replaced with lysine & B29 lysine replaced with proline Aspart: B28 proline replaced with aspartic acid Intermediate-acting (NPH/Isophane Insulin) Onset: 1-2 hours Peak: 4-12 hours Duration: 12-18 hours Delivery: Subcutaneous, once or twice per day Long-acting (Glargine & Detemir) Glargine: Stabilised at pH 4, delayed absorption Detemir: Enhances albumin binding, extended action Onset: 1-2 hours Peak: No distinct peak Duration: 24+ hours Delivery: Subcutaneous, once or twice per day Premixed Insulin Combination of short-acting and intermediate-acting insulin Onset: Varies Peak: Varies Duration: Varies Delivery: Subcutaneous, typically before meals

Question 113

What are the key points regarding inhaled insulin?

Answer 113

Rapid-acting Useful for those with needle phobia Can help with lipodystrophy (skin changes due to repeated insulin injections) Not readily available on NHS FDA approved in 2014 Requires high insulin doses Risk of bronchospasm (tightening of the airways) Potential increased risk of lung cancer (under investigation)

Question 114

What factors affect the pharmacokinetics of insulin absorption?

Answer 114

Injection site: Blood flow varies across different sites, influencing absorption speed. Massage: Massaging the injection site speeds up absorption. Insulin type: Different types (e.g., long-acting vs rapid-acting) have different absorption rates. Dose: A high dose delays the onset of action and prolongs the duration. Temperature: Heat increases absorption, while cold decreases it.

Question 115

How is insulin eliminated in the body?

Answer 115

Endogenous insulin: 50-60% is eliminated by the liver. ~35-45% is eliminated by the kidneys. Exogenous insulin: ~30-40% is eliminated by the liver. ~60% is eliminated by the kidneys.

Question 116

What are the key points regarding diabetes and its management?

Answer 116

Diabetes refers to a group of diseases, including Type 1 and Type 2 diabetes. The pancreatic islets produce hormones like insulin and glucagon, which regulate glucose homeostasis. Insulin promotes glucose uptake and glycogen synthesis. Type 2 Diabetes Mellitus (T2DM) involves a combination of genetic and environmental factors, and is treated with various oral or injectable medications. Type 1 Diabetes Mellitus (T1DM) is an autoimmune condition where the body attacks its own insulin-producing cells. T1DM is managed with insulin, which is available in various preparations (e.g., rapid, intermediate, long-acting).

Question 117

What are the physiological mechanisms that control blood glucose levels in the body?

Answer 117

Insulin is released from β cells in the pancreas when blood glucose is high, promoting glucose uptake into cells and glycogen synthesis in the liver and muscles. Glucagon is released from α cells in the pancreas when blood glucose is low, stimulating glycogen breakdown (glycogenolysis) and glucose production (gluconeogenesis) in the liver. Other hormones, such as epinephrine, cortisol, and growth hormone, also play a role in increasing blood glucose during stress or fasting.

Question 118

What are the main forms and causes of diabetes mellitus and the options for pharmacological management? A:

Answer 118

Type 1 Diabetes Mellitus (T1DM): An autoimmune condition where the immune system destroys insulin-producing β cells in the pancreas, leading to insulin deficiency. Managed with insulin therapy. Type 2 Diabetes Mellitus (T2DM): Insulin resistance in target tissues (muscles, liver, adipose) with eventual pancreatic β cell dysfunction. Managed with lifestyle changes, oral hypoglycaemic agents, and sometimes insulin therapy. Gestational Diabetes Mellitus (GDM): Occurs during pregnancy, usually in the 2nd/3rd trimester, due to insulin resistance. Managed with diet and insulin if necessary. Pharmacological management options include oral hypoglycaemic agents (e.g., metformin, sulfonylureas, SGLT2 inhibitors, DPP-4 inhibitors) and injectable therapies (e.g., insulin, GLP-1 agonists).

Question 119

How do insulin, glucagon, and commonly used oral hypoglycaemic agents compare in the control of blood glucose?

Answer 119

Insulin: Lowers blood glucose by facilitating glucose uptake into cells and glycogen synthesis in liver and muscle. Glucagon: Increases blood glucose by promoting glycogen breakdown and gluconeogenesis in the liver. Oral hypoglycaemic agents: Metformin: Reduces hepatic glucose production and increases insulin sensitivity. Sulfonylureas: Stimulate insulin release from pancreatic β cells. SGLT2 inhibitors: Increase glucose excretion in urine by inhibiting sodium-glucose co-transporter 2 in the kidneys. DPP-4 inhibitors: Enhance incretin effect, increasing insulin secretion and decreasing glucagon release.

Question 120

How do different modes of insulin management compare?

Answer 120

Multiple Daily Injections (MDI): Involves rapid-acting insulin at meals and long-acting insulin once or twice daily. Allows flexibility in timing and doses but requires careful management. Insulin Pump: Provides continuous subcutaneous insulin delivery, with basal rates and bolus doses controlled by the user. Offers more precise control but is more invasive and costly. Insulin Inhalers: Rapid-acting insulin delivered via inhalation, suitable for patients with needle phobia but associated with risks like bronchospasm and lung cancer. Insulin Pens: Convenient for subcutaneous injections with a pre-filled insulin cartridge, offering ease of use and portability.