GI Physiology - Glucose Metabolism

Question 1

How is glucose absorbed from the GI tract?

Answer 1

80% by passive diffusion
20% by active transport: sodium-glucose co-transport mechanism

Question 2

How is blood sugar controled? What other factors affect blood sugar?

Answer 2

Endocrine control of the liver

Insulin
Increases glucose uptake into cells
Increases glycogen synthesis
Reduces glycogenolysis
Reduces gluconeogenesis

Glucagon
Reduces glycolysis - causes glycolysis intermediary molecules to be shunted into glyconeogenesis pathway
Increases gluconeogenesis
Increases glycogenolysis
Stimulates lipase in fatty tissue - breaks down fat to fatty acids & glycerol - which can undergo gluconeogenesis
Glucagon also stimulates insulin, growth hormone & somatostatin release
Positive chronotropy & inotropy - used in beta-blocker toxicity

Steroids - reduce glucose uptake and usage in cells
Growth hormone - inhibits insulin
Adrenaline & other catecholamines - stimulate glyconeogenesis and reduce glucose uptake
Thyroid hormone - increases glucose uptake, glycolysis, gluconeogenesis and absorption from the gut
Oestrogen & Progesterone - can lead to a degree of insulin resistance

Question 3

How is insulin produced & how does it work?

Clarify duodenum vs bloodstream

Answer 3

Polypeptide anabolic hormone, produced by beta cells in pancreatic islets of Langerhans

Secreted into the duodenum contniously, increasing in production in reponse to raised blood sugar, amino acids, glucagon, gut hormones and the autonomic nervous system.

Inhibited by catecholamines stimulating α2 receptors and somatostatin

Acts on tyrosine kinase receptors in muscle & adipose cells, recruiting GLUT-4 proteins to the membrane.

In the liver, it doesn’t alter membrane permeability to glucose, but stimulates processes that consume glucose, driving a concentration gradient into the liver

Question 4

What are insulin’s effects?

Answer 4

Increases glucose (and potassium) uptake from blood
Increased glycogen synthesis
Reduced gluconeogenesis and glycogenolysis
Reduced hepatic release of glucose
Anabolism - enhanced protein storage and production
Increased fat synthesis
Reduced ketone production

Question 5

What hormonal changes occur in hypoglycaemia?

Answer 5

Pancreatic beta cells detect low blood sugar and reduce insulin secretion

Pancreatic alpha cells increase glucagon secretion - a polypeptide hormone that promotes catabolism, particularly in the liver.

Release of glucagon is stimulated by hypoglycaemia, stress, hunger, exercise, gastrin, secretin and cholecystokinin

Question 6

Discuss Glucagon

Answer 6

Catabolic 29 amino-acid peptide hormone,

Made by alpha cells in pancreatic islets, acts via cAMP

Stimulated by
Hypoglycaemia, amino acids, salbutamol, acetylcholine, stress

Inhibited by
Hyperglycaemia, fatty acids, insulin, somatostatin, alpha agonists

Effects
Glycogenolysis, glyconeogenesis
β oxidation of fatty acids & lipolysis
Increased catacholamine release
Positive inotropy

Question 7

Discuss somatostatin

Answer 7

Produced by δ cells in pancreas, also produced in hypothalamus.

Inhibits both insulin and glucagon release

Inhibits stomach acid production

Relaxes gallbladder

Also acts as neurotransmitter in substantia gelatinosa

Question 8

How can a cell produce energy?

Answer 8

Through production of the energy intermediate adenosine triphosphate (ATP) through a series of redox reactions.

Glycolysis
Does not require oxygen or produce CO2, and occurs in cytoplasm.
Produces 2 molecules of pyruvate per glucose
2ATP & 2NADH (which is recycled by mitochondria in aerobic conditions. Otherwise NAD is recycled by converting pyruvate to lactate)

Proteolysis & Lipolysis

Krebs Cycle
Occurs within mitochondria, can use pyruvate, ketones and Acetyl CoA.
No direct oxygen consumption, but high NAD requirement means it only functions when ETC is working.
Produced CO2, NADH and FADH.

Oxidative phosphorylation
Electron transport chain in mitochondria, with up to 38 ATP per glucose molecule