Control of Blood Glucose Flashcards
Glucose enters cells via SGLTs and GLUTs, what are SGLTs?
Rely on secondary active transport
SGLT1: glucose absorption from gut
SGLT1, SGLT2: glucose reabsorption from kidney (PCT)
Glucose enters cells via SGLTs and GLUTs, what are GLUTs?
GLUT 1 (and 3: brain, erythrocytes): high glucose affinity, so constantly uptake at 2-6 mM GLUT 2 (liver, kidney, pancreas, gut): low affinity, so rate of glucose uptake is related to extracellar glucose conc- useful in tissues which sense glucose levels GLUT 4 (muscle and adipose tissue) – medium affinity. Insulin-dependent uptake of glucose into cells
Desscribe the pancreatic islets of Langerhans and identify their cell types and secretions
Islets of Langerhans are clusters of endocrine cells surrounded by exocrine pancreas
α-cells (A cells) secrete glucagon
β-cells (B cells) secrete insulin
Delta δ-cells secrete somatostatin- regulates both insulin and glucagon secretion
Describe the synthesis of insulin
The initial polypeptide is called pre-proinsulin and its signal sequence is first removed.
This proinsulin moves to the rER, and then Golgi apparatus
Peptidases break off the C peptide leaving an A and B chain linked by disulphide bonds.
1 mole of C-peptide is secreted for each mole of insulin
C-peptide is inert, so a good index of insulin secretion.
How is insulin secreted?
Insulin is produced and secreted in the pancreatic islet from the B cells and then drains into the circulation
Pancreas supplied by branches of the coeliac, SM, and splenic arteries.
The venous drainage of the pancreas is into the portal system. This means most secreted insulin is metabolized by the liver in it’s first pass; the remainder is diluted in the peripheral circulation
Draw a diagram to show the factors regulating insulin secretion
somatostatin and alpha adrenergic symp stimulation inhibits (-) insulin release
Draw a diagram to show the factors regulating glucagon secretion
How do β cells sense rise in glucose?
Glucose enters the beta cell via the GLUT2 transporter.
Glucose enters glycolysis/krebs to make ATP, so increasing intracellular ATP.
On the beta cell membrane hay a K ATP Channel. It’s a potassium channel that is closed by ATP.
So the more glucose, the more ATP, the more closed channels we have.
Closed channels reduce K efflux, inducing depolarisation which activates vgccs.
Rise in intracellular Ca leads to insulin release
How do insulin receptors promote lipogenesis?
acetyl-CoA carboxylase (ACC) starts off lipogenesis by converting acetyl CoA to malonly CoA.
This is inhibited by PKA, which depends on cAMP for its activity.
Insulin binding leads to a decrease in cAMP levels, reducing PKA activity, releasing ACC from inhibition, thereby promoting lipogenesis.
What is the incretin effect?
Hay a much greater insulin response when glucose enters circulation via the oral route than when the same levels are directly infused into the blood
What is the physiology and reasoning behind the incretin effect?
Food ingestion releases incretin gut hormones. The incretins: glucagon-like peptide-1 (GLP-1) and GIP
These bind to beta, alpha and GLP1 receptors which boosts insulin production so that more glucose is taken up by cells
Another effect is that it acts on the liver to decrease glucose production
The incretins are rapidly degraded by DPP-4 enzyme
What is central is DM diagnosis?
Random plasma glucose ≥ 11.1 mmol L-1
Fasting plasma glucose ≥ 7.0 mmol L-1
Oral glucose tolerance test (OGTT) ≥ 11.1 mmol L-1
Give some drugs for the treatment of DM type 2
- *Metformin**: Decreases gluconeogenesis
- *Sulfonylureas**: bind and close KATP channels, depolarize B cell releasing insulin
- *SGLT2 inhibitors**: promote glucose excretion via kidney
- *Incretin targeting drugs**: potentiate insulin release in response to rising plasma glucose
What type of complication is retinopathy in DM?
Microvascular: directly related to glucose toxicity. Type-1: rare.
Type-2: Can be present at diagnosis. Increased incidence of macular oedema
Risk Factors for retinopathy inc poor glycaemic control, genetic factors, high bp, smoking
What type of complication is neuropathy in DM?
Microvascular, associated with the duration of DM
High glucose can injure nerves throughout the body, most often nerves in the legs and feet.
Peak incidence after 15-20 years, followed by a steady decline after 30-40 years
Risk Factors: Age at onset, poor glycaemic control, genetics, BP, Smoking
How would you treat and prevent diabetic nephropathy?
This is a microvascular complication
