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Year1-Endocrinology-Mubarak > Insulin secretion and intermediate metabolism > Flashcards

Insulin secretion and intermediate metabolism Flashcards

1
Q

List 9 effects of insulin on the body.

A
  • Decrease Hepatic Glucose Output.
  • Increase muscle glucose uptake.
  • Decrease proteolysis
  • Decrease Ketogenesis
  • Growth
  • Vascular Effects
  • Ovarian Function
  • Clotting-PAI-1
  • Energy Expenditure
  • relation to leptin.

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2
Q

What is GLUT 4?

A

G LUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle (skeletal and cardiac).

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3
Q

In which tissue is GLUT-4 mostly found?

A

Muscle and adipose

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4
Q

How much of an increase do GLUT 4 have on glucose uptake?

A

7x

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5
Q

Draw a diagram showing how insulin causes GLUT 4 to enter cells?

A

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6
Q

List the effects of Insulin on proteins and amino acids

A

Increased amino acid transport. Increased protein synthesis.

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7
Q

What usually is the biggest fear for type 1 diabetic patients besides the secondary effects iof diabetes?

A

Hypoglyceamia Early signs and symptoms of diabetic hypoglycemia include: Shakiness Dizziness Sweating Hunger Irritability or moodiness Anxiety or nervousness Headache

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8
Q

List 4 hormones that increase glucose production?

A

Cortisol Catecholamines- epinephrine (adrenaline), norepinephrine (noradrenaline). Somatotrophin Cortisol

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9
Q

What is Type 1 diabetes defined as?

A

T1DM is defined as elevated glucose where insulin is required to prevent ketoacidosis

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10
Q

What illnesses is type 2 diabetes related to?

A

hypertension and dyslipidaemia

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11
Q

List some of the complications of diabetes?

A

Diabetic retinopathy

Nephropathy

Heart attacks

Stroke

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12
Q

What range does the glucose level have to fall under to have hypoglyceamia?

A

If blood glucose falls below 4.0-5.5mM (hypoglycaemia) - then brain function is increasingly impaired.

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13
Q

What level does the glucose level have to drop to become unconcious, in a coma and die?

A

If blood glucose falls below 2mM it could lead to unconsciousness, coma and death.

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14
Q

Why do cells in the pancreas have gap junctions?

A

Cells in the pancreas have Gap Junctions which allow the hormones to have an effect on adjacent cells

  • PARACRINE EFFECT

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15
Q

What cells are found in the illets of langerhan?

A

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16
Q

What do delta cells do?

A

Delta cells (D cells) secrete the hormone somatostatin.

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17
Q

What does somatostatin do?

A

In the hypothalamus, it regulates the secretion of hormones coming from the pituitary gland, including growth hormone and thyroid stimulating hormone.

In the pancreas, somatostatin inhibits the secretion of pancreatic hormones, including glucagon and insulin. add pic

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18
Q

list all of the effects of insulin?

A

Insulin also prevents the break down of protein.

Insulin stops lipolysis and increases lipogenesis.

Without glucose, some amino acids can regulate insulin secretion

Some gastrointestinal hormones increase insulin secretion - this is important physiologically because before the food we eat even affects blood glucose, the food in our gut is making us produce insulin.

In particular, Glucagon Like Peptide makes us produce insulin .

There is neurological control of beta cells: Sympathetic Stimulation - switches off insulin to increase blood glucose concentration

Parasympathetic Stimulation - increases insulin secretion

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19
Q

State the Neural Regulation of insulin?

A

There is neurological control of beta cells:

Sympathetic Stimulation - switches off insulin to increase blood glucose concentration

Parasympathetic Stimulation - increases insulin secretion

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20
Q

How does the GI increase insulin secretion?

A

Some gastrointestinal hormones increase insulin secretion - this is important physiologically because before the food we eat even affects blood glucose, the food in our gut is making us produce insulin.

In particular, Glucagon Like Peptide makes us produce insulin .

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21
Q

How does insulin effect fat metabolism?

A

Decreased lipolysis Increased lipogenesis

22
Q

How does insulin effect protein metabolism and amino acids?

A

Increase amino acid transport into cells and increases protein synthesis.

23
Q

What substance can increase B cell activity besides glucose, hormones.

A

Amino acids

24
Q

Draw a mindmap of the metabolic effects of insulin? Include the factoes that inhibit and stimulate insulin release?

A

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25
Q

How does inslin effect heptocytes in terms of transporters, glucose genesis and glycogen metabolism?

A

Increased glycogenesis. Increased glycolysis. Increased glucose transport into cells via GLUT4.

26
Q

List all the factors effecting glucagon secretion?

A

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Stimulate: Sympathetic activity.

Parasympathetic activity

Certain GI hormones

Certain amino acids lower the glucose concentration

Inhibit: Insulin Somatostatin

27
Q

List the effects of glucagon?

A

INCREASED HEPATIC GLUCOSE OUTPUT

Glucagon generally elevates the concentration of glucose in the blood by promoting gluconeogenesis and glycogenolysis [7].

Glucagon also decreases fatty acid synthesis in adipose tissue and the liver, as well as promoting lipolysis in these tissues, which causes them to release fatty acids into circulation where they can be catabolised to generate energy in tissues such as skeletal muscle when required [8].

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28
Q

What is the rate determining step that regulates insulin secretion?

A

Glucokinase is the Rate Determining Step that regulates insulin secretion

29
Q

How does the pancrease decide what the plasma glucose is?

A

The sensing of glucose concentration is through GLUCOKINASE. add pic

30
Q

What is the function of GLUT 2 ?

A

Allows glucose to enter the cell without dependance on insulin. GLUT 2 is found in Beta cells and is not insulin sensitive

31
Q

List the steps of pre-pro insulin to the final products

A

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32
Q

What substance is made with insulin? It is bound to it in proinsulin

A

C-peptide

33
Q

Insulin has a short half life and degrades quickly in blood container bottles making it difficult to measure the blood insulin concentration. How is this problem solved?

A

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

34
Q

What is this molecule? add pic

A

Insulin

35
Q

What is always released with insulin in the pancreas?

A

C-peptide

36
Q

How can you tell if a patient is taking external sources of insulin or if the body is secreting the insulin by itself?

A

Measure the C-peptide

37
Q

What are the steps for insulin release?

A

add pic Glucose enters through Glut 2.

The ATP produced blocks the ATP sensitive potassium channels.

This leads to the opening of voltage dependent calcium channels.

Calcium rushes into the beta cell and insulin is secreted.

38
Q

””

A

There is stored insulin and manufacture of insulin over two hours to deal with that meal. People with type 2 diabetes can make insulin but not enough all at once. Meaning that if we can prolong glucose exposure they can make enough insulin. This is another measure to control glucose concentration.

39
Q

What is the incretin effect?

A

Incretin Effect - food stimulates more insulin secretion if given orally rather than intravenously.

The graph: When we eat a meal and there is food in our intestine we start producing insulin In this experiment someone is given a 50g oral glucose load and a matched intravenous infusion of glucose to cause exactly the same glucose profile

When given oral glucose, he makes considerably more insulin - this is the incretin effect add pic

40
Q

What is Glucagon like peptide-1 (GLP-1) secreted in response to?

A

Secreted in response to nutrients in gut

41
Q

What gene codes for GLP-1?

A

proglucagon gene

42
Q

What does GLP-1 do?

A

Stimulates insulin, suppresses glucagon Makes you feel full

43
Q

What cells produce GLP-1?

A

L cells

44
Q

What enzyme degrades GLP-1 and comment on its half life?

A

Short half life due to rapid degredation from enzyme dipeptidyl peptidase-4 (DPPG-4 inhibitor is a drug the prolongs GLP-1 effects).

45
Q

Describe the graph below add pic.

A

The normal person has an intravenous glucose load which makes him produce a lot of insulin instantly .

The person with T2DM has next to no first phase insulin - the insulin is made later on

First phase insulin release is important is important in switching off liver glucose production .

If someone has an oral glucose load you don’t see the first phase because it’s over 30 mins .

Type 2 don’t have stores of glucose.

Prolonging calorie exposure - complex carbohydrates. Release a steady amount of glucose.

46
Q

What causes insulin resistance?

A

Insulin resistance is NOT caused by the receptor not being able to recognise insulin or due to the transmembrane portion of the receptor not working. Insulin resistance lies in the post receptor cytoplasmic elements of insulin function.

47
Q

Is insulin an extracellular or intracellular hormone?

A

Extracellular

48
Q

What happens when insulin binds to its receptor?

A

Insulin is a protein/polypeptide hormone which does not cross membranes .

The alpha subunit of the insulin receptor recognises the 3D shape of insulin which causes a conformational change in the beta subunits which cross the membrane - this has a metabolic effect on glucose, amino acids and fatty acids.

It also affect growth (mitogenic pathway).

Phosphorylation of beta subunits is important in recruiting substrates which go on to have effects on the metabolic pathway. add pic

Year1-Endocrinology-Mubarak (12 decks)

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