Flashcards in Diabetes Physiology Deck (90):
What mechanism does the glucose transporter use to get glucose into the cell?
Facilitated diffusion (no ATP needed)
What type of hormone are insulin, glucagon and somatostatin?
Each glucose molecule produces how many acetyl-coA molecules?
(So two cycles of the krebs cycle are needed per glucose molecule)
Each molecule of glucose produces how many ATP molecules during aerobic respiration?
What causes fruity smelling breath in T1DM patients?
Ketones in the breath (Pair drops/ nail varnish remover)
Requires urgent hospital admission
What does a patient have to do to prepare for a fasting glucose test?
Drink nothing but water and eat nothing
For 8-10hours before the test
Which cells secrete GIP?
K cells in duodenum
Which cells secrete GLP-1?
L cells of ileum
What is the incretin effect?
Insulin response to oral glucose is greater than the response to IV glucose. GIP and GLP-1 peptide hormones are released from the duodenum and ileum respectively and act on Bcells in the pancreas (Decreased in T2DM)
What is the NICE recommended treatment for T2DM?
Add sulfonylurea (or DPP-4 if high hypoglycemic risk)
Add thiazolidinedione or insulin
Increase insulin dose
Why do diabetic patients get dehydrated?
Because as glucose is lost in urine water is pulled out (so more water lost) osmotically
What is the effect on insulin on potassium?
Closes K+ channels
So K+ stuck inside the cell
Name 3 examples where testing HbA1c levels would not be accurate?
Which cells produce the hormone released during hypoglycaemia?
Alpha cells of pancreas
Which enzyme converts glucose to glucose-6-phosphate?
Injury to which cells in the pancreas can lead to type I diabetes?
Which of the glucose transporters are insulin dependent?
Which substance is normally used to measure GFR?
What is the name for clusters of endocrine cells in the pancreas and how are the distributed?
Islets of langerhans
Scattered amoungst exocrine pancreatic acini
What % of pancreatic cells are endocrine?
What are the 4 types of endocrine cell in the pancreas and what do they each release?
Alpha (20%)- Glucagon
Beta (70%)- Insulin
Delta (8%)- Somatostatin
F cells (2%)- Pancreatic polypetide
What is the most common endocrine cell in the pancreas and what does it release?
What is glucagon and by what mechanism does it act on the cell?
A peptide hormone which increases blood sugar
Activates adenyl cyclase and increases cAMP
What metabolic processes are increased by high levels of glucagon?
What can inhibit insulin secretion?
What is insulin and by what mechanism does it act on the cell?
A peptide hormone which tries to decrease blood sugar levels
Activates surface receptor which activates a tyrosine kinase (attaches phosphate)
Which hormone can inhibit glucagon secretion and where is that hormone secreted from?
From Delta cells in pancreas
What is the role of F cells in the pancreas and what stimulates them?
Produce the hormone pancreatic polypeptide
(Regulates pancreatic enzyme release, GI absorption and gall bladder contraction)
- Stimulated by PNS/ protein rich meals
What stimulates pancreatic Bcells to release insulin? (4)
High blood sugar levels
AA's like arginine and leucine
Which receptors on pancreatic Beta cells detect blood glucose levels?
Which glucose receptors are found mainly on neurons and in the placenta?
Which of the glucose transports is insulin regulated?
What is the GLUT-5 transporter and where is it found?
A fructose transporter
Found in small intestine enterocyte cells
What controls how many GLUT-1 receptors are on the cell membrane?
Levels in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels.
Which glucose transport is bi-directional?
(Mainly renal, liver and pancreatic cells)
Where are GLUT-1 transporters mainly distributed?
Is widely distributed in fetal tissues
In adult mainly in erythrocytes and BBB
Where is the GLUT-4 transporter mainly located?
Adipose and striated muscle
How are GLUT-4 transporters activated?
Insulin binds to the insulin receptor in its dimeric form and activates the receptor's tyrosine-kinase domain, a signal cascade occurs and then GLUT-4 is transporter to the membrane
What happens to the glucose transporter when it contacts a glucose molecule?
Undergoes a conformation change
This allows glucose to pass in
What metabolic processes are upregulated by increased levels of insulin?
Increased glucose uptake in cells (GLUT-4)
Glycogenosis (Storing glucose as glycogen)
Glycolysis (Breakdown of glucose to pyruvate)
Amino acid absorbtion/ protein synthesis/ triglyceride formation
What is another name for somatostatin?
Growth hormone inhibting hormone (GH-IH)
What is the function of the delta cells in the pancreas?
What is the action of somatostatin?
Insulin/ glucagon/ secretin/ CCK/ gastrin/ motilin
Uses G-coupled receptors
What is the absorbtive state and what is it's primary hormone?
Approx 4 hours after each meal
Where nutrient absorption occurs
Regulated by insulin (body is taking in and using glucose to manufacture proteins/ lipids)
What process happen during the absorptive state?
Glycogenesis (Glucose stored as glycogen)
Glycolysis (Glucose broken down into AA's)
AA's to protein / triglyceride formation
Acetyl-CoA to FA's / Pyruvate to AA's
What is the name of the first substance in the Kreb's (citric acid cycle)
What is the post-absorptive state?
When nutrients are not being absorbed so body uses up stores
What key hormones regulate the post-absorptive state?
Glucagon/ GH/ adrenaline/ glucocorticoids
What glucose related processes happen in the post-absorptive state?
Glycogenolysis (Glycogen to glucose)
Gluconeogenesis (AA/ glycerol to Pyruvate to glucose)
What lipid/ protein related processes happen in the post-absorptive state?
Lipolysis- Triglycerides broken down
Lipid metabolism- FA's converted to acetyl-coA
AA metabolism- AA's converted to pyruvate
What is the name for the process by which glucose is turned into pyruvate?
What is the name for the process by which glycogen is broken down to glucose?
What is the name for the process by which triglycerides are broken into FA's and glycerol?
What is the name for the process by which by which pyruvate is converted into glucose?
What happens to amino acids during the post-absorptive state?
Released from liver
Metabolised into pyruvate
What is the electron transport chain?
NADH/ FADH2 are oxidised and loose their electrons, which join with H+ from the krebs cycle and oxygen to produce H2O
Where does the process of the electron transport chain occur?
What initiates the Krebs/ citric acid/ TCA cycle?
Glucose is converted to 2 pyruvate molecules
Pyruvate is then oxidised to acetyl-coA
Acetyl-CoA is locked into krebs cycle
What is the net result of the Krebs/ citric acid/ TCA cycle?
Acetyl-CoA cycling round gives off ATP/ NADH/ FADH which are used by the electron transport chain to gain energy
Each molecule of glucose creates how many pyruvate molecules?
Each molecule of glucose results in how many krebs cycles?
What are the three ketone bodies?
How are ketone bodies produced?
When lipids/ proteins are used to create Acetyl-CoA for the krebs cycle (instead of glucose being used)
What happens to ketone bodies in circulation?
Liver CAN'T metabolise ketone bodies
So must circulate until taken up by peripheral cells and converted to Acetyl-CoA
How does ketoacidosis develop?
Increased ketone body production = ketosis
Ketones disolve in solution producing H+, this causes a pH drop = Ketonemia
Eventually this exceeds buffering capacity= ketoacidosis
Where is glycogen mainly stored in the body?
Liver and muscles
What is the composition of the insulin molecule?
Two amino acid chains linked by a disulfide bond
How is insulin secreted?
Preproinsulin is cleaved in the ER to proinsulin (three peptide chains). This is cleaved to insulin in the golgi apparatus and packaged into granules
What is C peptide?
The peptide cleaved off when proinsulin becomes insulin
What role can C-peptide play in patient monitoring?
Monitor how much endogenous insulin is being created in patients on insulin treatment
10% of the secretion of Bcells are what?
Proinsulin and C peptide
How long does insulin circulate in the blood and how does this come to an end?
Half life of about 6mins
Degraded by insulinase mainly in the liver (but also kidney and muscle)
What is the composition of the insulin receptor?
4 (2 alpha/2beta) subunits linked by disulfide bonds
Where does insulin bind on the insulin receptor? What happens after it binds?
To the alpha subunit
Receptor is phosphorylated, this acitvates tyrosine kinase which via messenger cascades results in GLUT 4 up-regulation
Name 4 effects of insulin?
Increases cell uptake of glucose
Makes cell more permeable to AA's/ ions
Increased cell metabolic rate
What happens to muscle fibres when exercising (in relation to glucose)?
Muscle fibres become more permeable to glucose (even without insulin)
Which transporters does glucose enter the Bcell via?
How does glucose stimulate insulin release in the Bcell?
Glucose in via GLUT-2 transporter,
Phosphorylated to gluc-6-phosphate by hexokinase
G-6-P is oxidised to ATP, which opens K+ATPase channels, causing calcium influx and fusion of insulin vesicles with the membrane
Which agents inhibit B-cell release of insulin?
Somatostatin and noradrenaline
Which hormones potentiate the release of insulin (when under glucose stimulation)?
Gastrin/ secretin/ CCK can cause an anticipatory release whilst waiting for glucose/ AA absorption
Growth hormone and cortisol are secreted more under which glucose linked conditions?
(they both inhibit cellular glucose utilization and promote fat use instead)
What effect does somatostatin have on glucagon and insulin?
Inhibits their secretion
T1DM is an autoimmune disease charecterised by Bcell destruction whereas T2DM is...
A combination of peripheral resistance to insulin and an inadequate secretory response
What are the main T-cells involved in the destruction of Bcells in T1DM?
How can HbA1c levels be used to predict diabetes severity?
Glycosated Hb can be a predictor of macrovascular complications later on
What is the pathophysiology of diabetic retinopathy?
Hyperglycemia stimulates intracellular activation of Protein Kinase C
What is the pathogenesis of macrovascular changes in diabetes?
Hyaline thickening of wall of arterioles and narrowing of lumen
How do the membranes of diabetic patients differ to those in non-diabetics?
More leaky to protein
(underlies diabetic nephropathy and retinopathy)
Which enzyme increases fatty acid levels in times of insulin deficiency?