Insulin Secretion and Intermediary Metabolism (4)

Question 1

what hormones are involved in increasing blood glucose levels

Answer 1

glucagon. catecholamines. somatotrophin. cortisol

Question 2

what is T1DM

Answer 2

defined as elevated glucose where insulin is required to prevent ketoacidosis

Question 3

what is T2DM

Answer 3

more common than T1DM and is a considerable health burden. It is defined in terms of glucose but is also related to hypertension and dyslipidaemia

Question 4

What are the complications of diabetes

Answer 4

Diabetic retinopathy. Nephropathy. Heart attacks. Stroke

Question 5

why is glucose important

Answer 5

very important energy substrate, particularly for the CNS which mainly respires glucose under normal conditions.

Question 6

What happens if blood glucose falls below 4.0-5.5mM (hypoglycaemia)

Answer 6

brain function is increasingly impaired.

Question 7

what happens if blood glucose falls below 2mM

Answer 7

could lead to unconsciousness, coma and death.

Question 8

what is most of the pancreas involved in (98%)

Answer 8

exocrine secretions via duct to small intestine

Question 9

what is the remaining 2% of the pancreas

Answer 9

Islets of Langerhans which are clumps of cells with a specific endocrine function.

Question 10

what do the beta cells of the islets of Langerhans do

Answer 10

secret insulin

Question 11

what do the delta cells of the islets of Langerhans do

Answer 11

secrete somatostatin

Question 12

what does somatostatin do

Answer 12

decrease the production of insulin and glucagon

Question 13

what does somatostatin do

Answer 13

decrease the production of insulin and glucagon (negative hormone). mainly paracrine effects.

Question 14

What is paracrine control

Answer 14

Cells in the pancreas have Gap Junctions which allow the hormones to have an effect on adjacent cells - paracrine effect. They allow small molecules to pass directly between cells. There are also small collections of fluid between cells formed by Tight Junctions.

Question 15

what does insulin do

Answer 15

stimulates growth and development in utero and child. decreases blood glucose (metabolic pathway)

Question 16

what does glucagon do

Answer 16

increases blood glucose

Question 17

What factors increase insulin secretion from beta cells

Answer 17

increase in blood glucose. certain amino acids, certain gastrointestinal hormones. glucagon from alpha cells. parasympathetic activity (beta receptors)

Question 18

what factors inhibit insulin secretion from beta cells

Answer 18

sympathetic activity (alpha cells) and somatostain from delta cells

Question 19

what are the effects of insulin release

Answer 19

increased aa transport and increased protein synthesis. decreased lipolysis and increased lipogenesis. increased glycogenesis and increased glycolysis. increased glucose transport into cells via GLUT4. decreased blood glucose.

Question 20

what factors stimulate glucagon secretion from alpha cells.

Answer 20

Certain GI hormones. Certain amino acids. sympathetic nervous activity. decreased blood glucose

Question 21

what are the effects of glucagon release

Answer 21

increased amino acid transport into liver and increased lipolysis –> increased gluconeogenesis –> increased blood glucose. increased hepatic glycogenolysis

Question 22

what factors inhibit glucagon secretion from alpha cells

Answer 22

Beta cells secreting insulin. parasympathetic nervous activity (alpha-receptors). Somatostatin

Question 23

What does glucokinase (aka hexokinase IV/the glucose sensor) do

Answer 23

Glucokinase is the Rate Determining Step that regulates insulin secretion. Glucose is transported into beta cell via GLUT 2. Glucose is converted to glucose-6-phosphate using Glucokinase, synthesising ATP  Via metabolic pathways. G6P results in insulin synthesis and release from the beta-islet cell 

Question 24

Synthesis of insulin

Answer 24

Insulin is a two chain (a and b) polypeptide hormone which is synthesised from pre-proinsulin in the ER. Removal of the pre-peptide leads to pro-insulin. Cleaved at amino acid 64 and 32. Cleavage produces c-peptide and the alpha and beta chains of insulin. A and B chains of insulin are held together by disulphide bonds and is transported to the Golgi apparatus. It is packaged into vesicles and proteolysis of the link between A and B chains occurs resulting in Insulin and C-Peptide



Question 25

How can measurments of c peptide be used to assess pancreatic function

Answer 25

The molar ratio of insulin to C peptide is 1:1 so by measuring C peptide you can measure endogenous insulin production and see if the beta cells are functioning. Insulin being released by the pancreas is always released with C peptide

Question 26

whow is insulin secreted

Answer 26

Glucose enters through GLUT2. Glucose –> G6P + ATP
ATP inhibits ATP dependent potassium channels causing depolarization. Voltage dependent calcium channels open and calcium enters beta cell. Then a calcium-calmodulin-dependent-kinase causes exocytosis of insulin vesicles

Question 27

What is the incretin effect

Answer 27

food stimulates more insulin secretion if given orally rather than intravenously

Question 28

What is glucagon like peptide-1 (GLP-1)

Answer 28

A gut hormone that mimics Glucagon and is secreted in response to specific nutrients in the gut. It stimulates insulin and suppresses glucagon. It also increases satiety. A transcription product of proglucagon gene, mostly from L cell. Short half life due to rapid degredation from dipeptidyl- peptidase 4.

Question 29

what is first phase insulin

Answer 29

stored insulin which is released directly after a meal. important in switching off liver glucose production 

Question 30

what is second phase insulin

Answer 30

newly synthesised insulin which is released over a couple of hours, and increases food storage (glycogenesis)

Question 31

describe the insulin receptor

Answer 31

The 2 extracellular alpha subunits- recognise and bind to insulin. 2 transmembrane beta subunits with tyrosine kinase domains. Binding of insulin causes a conformational change in tyrosine kinase domains. Also autophosphorylation
and cross -phosphorylation
of receptors occurs.  Conformation change leads to phosphorylation of cell protein substrates

Question 32

what are the three domains of the beta subunit

Answer 32

Extracellular associated with alpha subunit. Transmembrane. Intracellular with Tyrosine Kinase activity.