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what is metabolism?

Refers to all chemical reactions that occur within cells of the body


what is fuel metabolism (intermediary metabolism)?

Refers to reactions involving catabolism, anabolism and transformation of protein, carbohydrate (CHO) and fat


what hormones are fuel metabolism regulated by?

Insulin, glucagon, adrenaline, cortisol and growth hormone


what regulates metabolic rate?

thyroid hormone


what is glucose stored as?



what are endocrine glands made of?

islets of langerhans


what 4 major types of secretory cells do islets contain?

1) Alpha cells (glucagon)
2)Beta cells (insulin, proinsulin, C peptide and amylin)
3)Delta cells (somatostatin)
4) F cells (pancreatic polypetide )


what are the most abundant cells in the islet?

beta cells


where are beta cells located in the islet?

in the centre of the islet


what cells sit at the periphery of the islet?

alpha and delta cells


how do cells within the islet communicate?

gap and tight junction


what do the cells in islets receive external input from?

Both branches of the autonomic nervous system


what do beta cells do?

synthesise and secrete insulin


what is the structure of mature insulin?

2 peptide chains (A and B chains) joined by disulfide linkages.
The mature insulin molecule has a total of 51 AA:
21 on the A chain + 30 on the B chain


what does the secretory vesicle release into the blood when glucose stimulates the beta cell?

C peptide


what is the role of insulin during fasting and feeding?

integrates body fuel metabolism


Describe the events of insulin during fasting (post-absorptive period)

The beta cell secretes less insulin:
Lipids are mobilised from adipose tissue
Amino acids (AAs) are mobilised from muscle and other tissues
Lipids and AAs provide fuel for oxidation and act as pre-cursors for hepatic ketogenesis and gluconeogenesis, respectively


Describe the events of insulin during feeding (absorptive period)

The beta cell secretes more insulin:
Catabolism of endogenous fuel stores is inhibited
CHO, lipid and AA uptake by specific insulin-sensitive tissues is stimulated
(Insulin directs tissues to replenish fuel reserves that were used during periods of fasting)


what are the overall function of insulin?

Insulin maintains the [glucose]*blood within narrow limits
Helps provide the CNS with a constant supply of glucose for fuel to maintain cortical function


what are symptoms of hypoglycaemia?

confusion, seizures, coma


what are symptoms of hyperglycemia?

characteristic of the diabetic state: osmotic diuresis --> severe dehydration, hypotension and vascular collapse


what are glucose levels in an healthy individual?

-After an overnight fast: 4-5 mM
-Rises after a meal: does not exceed 10 mM


what do modest increases in plasma [glucose] provoke?

increase in insulin secretion and hence plasma insulin


why is insulin levels after glucose injected by IV much lower than that of insulin after glucose after oral digestion?

- 3 peptides : CCK, GLP-1 and GIP enhance insulin secretion

- all 3 are released in the GI tract in response to feeding


Describe the metabolism of glucose by the beta cell trigger insulin secretion.

-Glucose is taken up by pancreatic beta cells facilaitated by GLUT 2 – then undergoes glycolyiss

-Leads to increase in intraceullar ATP

-This closes ATP sensitive channels (potassium)-prevents loss of potassium ions from the cells – positive charge in cell

-Causes depolarisationm of membrane potential which
opens voltage dependant calcium channels , increase in interceullar calcium

-stimulates exocyotsis of the vesicles to release the insulin into the ECF and eventusally in the blood


what are the roles of the autonomic nervous system in insulin secretion?

Sympathetic stimulation inhibits insulin secretion

Parasympathetic stimulation stimulates insulin secretion (during feeding – cephalic phase)


what happens during exercise?

-suppresses insulin secretion
-Helps prevent excessive glucose uptake by muscle, which could lead to severe hypoglycemia (compromising the CNS)


what are the 3 principal target tissues for insulin?

1. liver (glucose stored as glycogen)
2. skeletal muscle (glucose stored are glycogen)
3. adipose tissue (stored as fat)


what are the actions of insulin in the liver?

Promotes the synthesis of glycogen
Inhibits glycogenolysis
Inhibits gluconeogenesis (at high plasma [insulin])

Promotes the storage of fats as triglycerides and inhibits the oxidation of fatty acids (therefore insulin causes the liver to burn CHOs preferentially).

Stimulates the synthesis of protein and simultaneously reduces the degradation of protein within the liver


what are the actions of insulin in skeletal muscle?

Stimulates glucose uptake via increased PM expression of GLUT4, an insulin-sensitive facilitative glucose transport protein (next slide)

Enhances conversion of glucose to glycogen

Increases glucose breakdown and oxidation (cells diminish fat utilisation, fatty acids stored as triglycerides)

Stimulates protein synthesis and slows protein degradation (preservation of protein mass)