Properties of Proinsulin and C-Peptide

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Questions and Answers

What is the half-life of insulin in plasma under normal conditions?

10-15 minutes

1-2 minutes

3-5 minutes (correct)

30-60 minutes

Which of the following organs are involved in insulin metabolism?

Kidney and pancreas

Liver, kidney and placenta (correct)

Liver and kidney

Pancreas and liver

What is the mechanism of insulin metabolism?

Insulin specific proteases and glutathione-insulin transhydrogenase (correct)

Insulin specific proteases only

Glutathione-insulin transhydrogenase only

None of the above

What is the function of glucagon?

To raise blood glucose levels Signup and view all the answers

Where is glucagon synthesized?

A cells of pancreatic islets Signup and view all the answers

How is glucagon inactivated?

By the liver, which removes the first two amino acids Signup and view all the answers

What is formed when proinsulin and insulin combine with zinc?

Hexamers Signup and view all the answers

What is released into the extracellular fluid when mature granules fuse with the plasma membrane?

Insulin and C-peptide Signup and view all the answers

Why may a radioimmunoassay for 'insulin' occasionally overestimate the bioactivity of 'insulin' presence in plasma?

Because proinsulin is released with insulin Signup and view all the answers

What is the location of the human insulin gene?

Short arm of chromosome 11 Signup and view all the answers

What is the primary physiological regulator of insulin secretion?

Glucose Signup and view all the answers

Which of the following hormones increases insulin secretion?

Growth hormone Signup and view all the answers

How much insulin does the human pancreas secrete daily?

40-50 units Signup and view all the answers

What is a characteristic of insulin metabolism?

Insulin is rapidly metabolized Signup and view all the answers

What is the typical time frame for the onset of ketoacidosis in patients with type 1 diabetes after withdrawing exogenous insulin therapy?

Within 48 h Signup and view all the answers

What is the typical age range for the onset of type 1 diabetes?

Childhood or puberty Signup and view all the answers

What triggers the autoimmune attack on pancreatic β-Cells in type 1 diabetes?

Unknown factor(s) Signup and view all the answers

What is the usual duration of the process of β-Cell destruction in type 1 diabetes?

Months Signup and view all the answers

What is the effect of an intercurrent illness on the onset of type 1 diabetes?

It unmasked the onset Signup and view all the answers

What is the result of the autoimmune attack on pancreatic β-Cells in type 1 diabetes?

Almost complete loss of insulin and C-peptide secretion Signup and view all the answers

What is associated with a high prevalence of type 1 diabetes?

Certain genetic markers Signup and view all the answers

What accounts for about half the genetic risk of type 1 diabetes?

Genes related to histocompatibility linked antigens (HLAs) and other markers Signup and view all the answers

What is the role of copper ions in dopamine β-monooxygenase?

To facilitate enzymatic activity Signup and view all the answers

What is the source of the hydroxyl oxygen in dopamine β-monooxygenase?

Molecular oxygen Signup and view all the answers

What is the initial and rate-limiting step in the synthesis of dopamine, norepinephrine, and epinephrine?

Tyrosine hydroxylase Signup and view all the answers

What is the function of Phenylethanolamine N-methyltransferase (PNMT)?

To methylate norepinephrine Signup and view all the answers

What is the primary metabolite of norepinephrine?

DHPG Signup and view all the answers

What is the enzyme responsible for the metabolism of DHPG?

COMT Signup and view all the answers

What is the predominant metabolite of norepinephrine in human CSF?

MHPG Signup and view all the answers

What is the therapeutic strategy for the treatment of depression?

Blockade of norepinephrine Signup and view all the answers

What is the neurotransmitter released at the surface of the adrenal medullary chromaffin cell?

Acetylcholine Signup and view all the answers

What is the effect of estrogens on Tyrosine concentration?

Decrease Signup and view all the answers

What is the primary function of the Substantia Nigra region in the brain?

Motor control and reward mechanisms Signup and view all the answers

What is the role of Dopamine produced in the Adrenal Medulla?

Regulation of blood pressure and heart rate Signup and view all the answers

What is the precursor for the synthesis of catecholamines?

L-tyrosine Signup and view all the answers

What is the role of Ventral Tegmental Area (VTA) in the brain?

Involved in motor control and reward mechanisms Signup and view all the answers

What is the result of the activation of the acetylcholine receptor on the chromaffin cell?

Release of epinephrine and norepinephrine Signup and view all the answers

What is the role of Tyrosine in the body?

Synthesis of catecholamines, melanine, thyroid hormones and quinoproteins Signup and view all the answers

Study Notes

Insulin and Proinsulin

Insulin and proinsulin combine with zinc to form hexamers.
Upon stimulation, mature granules fuse with the plasma membrane and release insulin and C-peptide into the extracellular fluid.
Proinsulin has a longer plasma half-life than insulin, which can lead to an overestimation of insulin bioactivity in radioimmunoassays.
C-peptide has no known biological role, but its immunoassay can distinguish between endogenous and exogenous insulin and quantify the former when anti-insulin antibodies are present.

Insulin Secretion and Regulation

Insulin secretion is precisely regulated, with the human pancreas secreting 40-50 units of insulin daily, representing 15-20% of the hormone stored in the secretory gland.
Glucose is the most important physiologic regulator of insulin secretion, with two proposed mechanisms:
Glucose combining with a receptor on the B cell membrane to activate the release mechanism.
Intracellular metabolites or metabolite flux through pathways (e.g., PPP, TCA cycle, glycolytic pathway) involved in insulin secretion.
Hormonal factors, such as growth hormone, cortisol, placental lactogen, estrigens, and progestins, as well as gastrointestinal hormones, can increase insulin secretion.

Insulin Metabolism

Insulin has no plasma carrier protein and has a half-life of 3-5 minutes in plasma under normal conditions.
The major organs involved in insulin metabolism are the liver, kidney, and placenta.
Insulin metabolism involves two enzyme systems:
Insulin-specific proteases found in many tissues, which are sulfhydryl-dependent and active at physiological pH.
Hepatic glutathione-insulin transhydrogenase, which reduces disulfide bonds and leads to rapid degradation of individual A and B chains.

Glucagon

Glucagon is an insulin antagonist, synthesized mainly in A cells of pancreatic islets.
Glucagon is a single-chain polypeptide (3,485 kDa) consisting of 29 amino acids, synthesized as a proglucagon precursor.
Glucagon circulates in plasma in its free form, without association with transport proteins.
Glucagon is inactivated by the liver, which removes the first two amino acids from the N-terminal end.

Diabetes Mellitus

Type 1 diabetes typically results from an autoimmune attack on pancreatic β-cells, with genetic susceptibility and possible environmental cofactors.
The onset of type 1 diabetes is usually during childhood or puberty, with symptoms developing suddenly.
Type 2 diabetes has a more gradual onset, often present many years before diagnosis.

Dopamine and Catecholamines

Dopamine is synthesized from the amino acid L-tyrosine, with a separate distribution in the brain, indicating its independent function as a neurotransmitter.
Tyrosine hydroxylase is the most important enzyme in catecholamine synthesis, being the initial and rate-limiting step in the synthesis of dopamine, norepinephrine, and pinephrine.
Dopamine is involved in motor control, reward mechanisms, and the production of other neurotransmitters.

Norepinephrine

Norepinephrine is synthesized from dopamine, with the addition of a β-hydroxyl group.
Norepinephrine is metabolized primarily to the alcohol metabolite, 3,4-dihydroxyphenylglycol (DHPG), and then further metabolized to 3-methoxy-4-hydroxyphenylglycol (MHPG).
Patterns of norepinephrine metabolites differ among animal species, with MHPG being the predominant metabolite in human CSF.

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Description

This quiz covers the properties of proinsulin and C-peptide, including their formation, release, and half-life. It also touches on the differences between proinsulin and insulin, and their roles in the body.