Lectures 13 & 14 - Pancreas and Glucose Metabolism Feb 5 & 7, 2025 Flashcards
1
Q
What are the two main types of glands in the pancreas?
A
Endocrine and exocrine glands.
The pancreas has both endocrine functions (hormone secretion) and exocrine functions (digestive enzyme secretion).
2
Q
What are pancreatic islets also known as?
A
Islets of Langerhans.
They are clusters of endocrine cells within the pancreas.
3
Q
What percentage of the pancreatic mass do the islets of Langerhans constitute?
A
1-2%.
4
Q
What is the main function of glucagon?
A
Increases blood glucose levels by promoting glycogenolysis in the liver.
5
Q
What are the three main ways pancreatic islets communicate with each other?
A
- Humoral communication
- Cell-cell communication
- Neural communication
6
Q
True or False: Cholinergic stimulation enhances insulin secretion.
A
True.
7
Q
What hormone is secreted by alpha cells in the pancreas?
A
Glucagon.
8
Q
What are the four types of secretory cells found in pancreatic islets?
A
- Alpha cells
- Beta cells
- Delta cells
- F-cells
9
Q
What hormone do beta cells secrete?
A
Insulin.
10
Q
What is the primary function of insulin?
A
Lowers blood glucose levels.
11
Q
What do delta cells secrete?
A
Somatostatin.
12
Q
What is the function of somatostatin?
A
Inhibits the secretion of multiple hormones, including insulin and glucagon.
13
Q
What is the role of pancreatic polypeptide secreted by F-cells?
A
Inhibits pancreatic digestive enzymes and intestinal motility.
14
Q
Fill in the blank: Insulin is a peptide hormone consisting of two straight chains linked by _______.
A
disulfide bridges.
15
Q
What does GLUT stand for?
A
Glucose transporters.
16
Q
Which GLUT transporter is primarily found in adipose tissue and skeletal muscles?
A
GLUT4.
17
Q
What factors stimulate insulin release?
A
- Elevated blood glucose levels
- Amino acids
- Fatty acids
- Glucagon
- Growth hormone
- Cortisol
- Vagal stimulation
- Gastric inhibitory peptide (GIP)
18
Q
What is the effect of somatostatin on insulin secretion?
A
Inhibits insulin secretion.
19
Q
What happens to KATP channels when glucose concentrations increase?
A
They close.
20
Q
True or False: Insulin is secreted primarily in response to elevated blood concentrations of glucose.
A
True.
21
Q
What is the composition of insulin secretion by beta cells?
A
About 5% is proinsulin and equimolar amounts of C-peptide.
22
Q
What are factors that inhibit insulin release?
A
- Somatostatin
- Alpha-adrenergic agonists
- Low glucose concentration
- Fasting
- Exercise
23
Q
What is the primary trigger for insulin exocytosis in beta cells?
A
Increased intracellular calcium levels.
24
Q
What percentage of pancreatic islet cells are beta cells?
A
About 70%.
25
What hormone is released during hypoglycemia?
Glucagon.
26
What is the role of glucose in insulin secretion?
Glucose is the major regulator of insulin secretion; a modest increase of glucose triggers a marked increase of plasma insulin.
27
What is the effect of oral glucose compared to intravenous glucose on insulin secretion?
Oral glucose is a more powerful stimulant for insulin secretion than intravenous infusion because it involves the gastric inhibitory peptide (GIP) hormone.
28
What are the two main types of diabetes mellitus?
* Type-1 diabetes mellitus (T1DM) - insulin dependent
* Type-2 diabetes mellitus (T2DM) - non-insulin dependent
29
What complications are associated with diabetes mellitus?
* Cardiomyopathy
* Nephropathy
* Neuropathy
* Retinopathy
30
What is a common characteristic of T1DM?
T1DM results from autoimmune destruction of insulin-producing beta-cells.
31
What characterizes Type-2 diabetes mellitus?
T2DM is characterized by peripheral insulin resistance and dysfunctional insulin secretion by pancreatic beta cells.
32
What are high levels of insulinoma antigen-2 autoantibodies indicative of?
They are common diagnostic features of Type-1 diabetes mellitus.
33
What is diabetic ketoacidosis?
Diabetic ketoacidosis is caused by significant reduction of insulin, especially in type-1 diabetes.
34
What metabolic change occurs in low insulin conditions?
The body enhances the metabolism of lipids leading to high levels of ketones.
35
What is the main pathophysiological feature shared by T1DM and T2DM?
Both conditions are associated with persistent hyperglycemia.
36
What is the function of the insulin receptor?
The insulin receptor is a catalytic receptor that phosphorylates tyrosine residues on itself and other proteins.
37
What happens when insulin binds to its receptor?
Ligand binding causes conformational changes that activate the tyrosine kinases on the β subunits.
38
What are the components of the insulin receptor?
The insulin receptor is a heterotetramer made up of two extracellular α-chains and two membrane-spanning β-chains.
39
What are insulin receptor substrates (IRS)?
IRS are a family of cytosolic proteins that are important links in the insulin signal transduction pathway.
40
How does insulin initiate its metabolic effects?
Insulin initiates its effects by binding to its receptor and activating the insulin signal transduction cascade.
41
What does the PI 3-kinase pathway lead to?
It leads to the translocation of GLUT4 into the plasma membrane and enhances glycogen synthesis.
42
Fill in the blank: The number of insulin receptors present on a target cell is determined by _______.
[receptor synthesis, endocytosis, degradation]
43
True or False: In a normal individual, the glucose response to insulin is maximal when only about 5% of the receptors are occupied.
True
44
What factors influence the ability of insulin to act on a target cell?
* The number of receptors present on the target cell
* The receptor's affinity for insulin
* The receptor's ability to transduce the insulin signal
45
What role does IRS-1 play in the body?
IRS-1 has a major role in skeletal muscle.
46
What is the relationship between insulin signaling defects and type 2 diabetes?
Defects in muscle IRS-1 have been reported in insulin-resistant type 2 diabetes.
47
What does MAPK activate downstream?
p90-S6 kinase
## Footnote
p90-S6 kinase phosphorylates various nuclear proteins, including protein phosphatase 1 (PP1)
48
What are the major sites where insulin exerts its effects?
* Liver
* Muscles
* Adipose tissue
49
What does insulin promote in the liver?
* Storage of glucose as glycogen
* Lipogenesis
* Stimulate protein metabolism
50
What actions does insulin have in muscle cells?
* Increase uptake of glucose via GLUT4
* Enhance conversion of glucose to glycogen
* Increase glucose breakdown
* Promote synthesis of proteins
51
Fill in the blank: Insulin promotes the storage of glucose as _______ in the liver.
glycogen
52
What effect does insulin have on adipose tissue?
* Increase uptake of glucose via GLUT4
* Stimulates breakdown of glucose
* Promotes formation of triglycerides
* Induces the synthesis of lipoprotein lipase
53
True or False: Insulin inhibits glycogen breakdown in the liver.
True
54
What is the role of C-peptide in insulin secretion?
C-peptide is secreted in equimolar amounts with insulin and has no biological function.
55
What are the early manifestations of hypoglycemia?
* Palpitations
* Tachycardia
* Diaphoresis
* Anxiety
* Hyperventilation
* Shakiness
* Weakness
* Hunger
* Nausea
56
What are the effects of glucagon on liver cells?
* Promotes net glycogen breakdown
* Promotes net gluconeogenesis
* Promotes the oxidation of fats
57
Fill in the blank: Insulin inhibits _______ in the liver.
gluconeogenesis
58
What is the effect of glucagon on glycolysis?
Glucagon inhibits glycolysis by reducing the activity of glucokinase, phosphofructokinase, and pyruvate kinase.
59
What is the role of nitric oxide in glucose metabolism?
Increases vasodilation and enhances glucose uptake.
60
What are the effects of hPL on the mother during pregnancy?
* Reduces maternal insulin sensitivity causing hyperglycemia
* Reduces maternal utilization of glucose
* Enhances maternal lipolysis
61
What are the microvascular complications of diabetes?
* Diabetic retinopathy
* Diabetic nephropathy
* Diabetic neuropathy
62
What does insulin promote in adipocytes?
* Glucose uptake via GLUT4
* Glycolysis leading to formation of α-glycerol phosphate
* Esterification of α-glycerol phosphate with fatty acids to form triglycerides
* Synthesis of LPL
63
True or False: Insulin promotes protein breakdown.
False
64
What are the effects of severe hyperglycemia?
* Kussmaul hyperventilation
* Stupor
* Coma
* Hypotension
* Cardiac arrhythmias
65
What does insulin do to fat oxidation?
Inhibits fat oxidation by increasing levels of malonyl CoA.
66
What is the relationship between glucagon and insulin in the liver?
Glucagon generally antagonizes the effects of insulin.
67
What is the effect of hPL on maternal insulin sensitivity?
Reduces maternal insulin sensitivity, causing hyperglycemia and gestational diabetes.
## Footnote
hPL stands for human placental lactogen, which plays a role in glucose metabolism during pregnancy.
68
What are the effects of hPL on maternal utilization of nutrients?
Reduces maternal utilization to ensure adequate fetal nutrition.
## Footnote
This mechanism helps prioritize the fetus's energy needs.
69
How does hPL affect maternal lipolysis?
Enhances maternal lipolysis.
## Footnote
Lipolysis is the breakdown of fats, which increases fatty acids available for energy.
70
What are the microvascular complications of diabetes?
* Diabetic retinopathy
* Diabetic nephropathy
* Diabetic neuropathy (peripheral nerve dysfunction)
## Footnote
Microvascular complications primarily affect small blood vessels and can lead to serious health issues.
71
What is the central mechanism in macrovascular disease related to diabetes?
The process of atherosclerosis, which leads to narrowing of arterial walls due to chronic inflammation.
## Footnote
Atherosclerosis is a significant risk factor for cardiovascular diseases.
72
What are the macrovascular complications of diabetes?
* Coronary artery disease/Heart disease
* Stroke
* Peripheral arterial disease
## Footnote
Macrovascular complications involve larger blood vessels and significantly increase the risk of cardiovascular events.
73
What is diabetic ketoacidosis?
A condition caused by significant reduction of insulin, especially in type-1 diabetes.
## Footnote
It can lead to severe metabolic disturbances and requires immediate medical attention.
74
What state may diabetic ketoacidosis lead to?
Diabetic coma, a condition of sleep-like state where a person is not conscious.
## Footnote
This is a medical emergency and can be life-threatening.
75
What causes the production of high levels of ketones in diabetic ketoacidosis?
Enhanced metabolism of lipids (fatty acids) due to low insulin levels.
## Footnote
Ketones are produced in the liver during low food intake or intense exercise.
76
When are ketones generally produced in the body?
During low food intake such as starvation or during intense exercise.
## Footnote
Ketones serve as an alternative energy source when glucose is scarce.
