Insulin and Fat Cells Overview

Questions and Answers

What is the primary physiological role of glucagon?

To increase glycogen synthesis

To promote fat storage in adipocytes

To stimulate glucose output from the liver (correct)

To enhance insulin secretion

Which factor stimulates the secretion of glucagon?

Increased insulin levels

High blood glucose concentration

Rise in serum amino acids such as arginine (correct)

Increased somatostatin levels

What is the effect of glucagon on glycolysis in the liver?

It increases glycolysis activity

It decreases glycolysis activity (correct)

It converts lactate to glucose

It has no effect on glycolysis

How is proglucagon primarily cleaved in the pancreatic α cells?

To yield glucagon and glucagon-related polypeptide (GRPP) Signup and view all the answers

What is the role of cortisol regarding glucagon secretion?

It stimulates glucagon secretion Signup and view all the answers

In what way does glucagon affect beta-oxidation?

It increases beta oxidation activity Signup and view all the answers

Which metabolic pathway is primarily increased by glucagon in the liver?

Gluconeogenesis Signup and view all the answers

What happens to oxaloacetate under the influence of glucagon?

It is utilized for gluconeogenesis instead of the citric acid cycle Signup and view all the answers

What characterizes Type 1 diabetes in relation to pancreatic beta cells?

There is destruction of pancreatic beta cells. Signup and view all the answers

Which process is inhibited by insulin to help regulate blood glucose levels?

Gluconeogenesis Signup and view all the answers

What accounts for the majority of diabetes cases?

Type 2 diabetes Signup and view all the answers

Which of the following tissues are primarily influenced by insulin for glucose uptake?

Skeletal muscle, liver, and adipose tissue Signup and view all the answers

What aspect of insulin action helps maintain a steady supply of glucose for energy?

Promotion of glycogen synthesis Signup and view all the answers

Which of the following is NOT a factor in Type 2 diabetes development?

Genetic mutations exclusively Signup and view all the answers

What role does insulin play in cellular processes?

It aids in cellular growth and differentiation. Signup and view all the answers

In what situation might secondary diabetes occur?

As a result of pancreatic tumors Signup and view all the answers

What is a consequence of advanced glycation end products (AGEs) in the vascular system?

Narrowing of smaller arteries Signup and view all the answers

What characterizes hyaline arteriolosclerosis in diabetics compared to nondiabetics?

More substantial amorphous thickening of arteriolar walls Signup and view all the answers

Which statement about diabetic neuropathy is true?

It can lead to sexual dysfunction and postural hypotension. Signup and view all the answers

What condition does diabetic microangiopathy mainly contribute to?

Increased leakage of plasma proteins in capillaries Signup and view all the answers

What role does hyperglycemia have in the activation of protein kinase C pathway?

It promotes increased susceptibility to coagulation. Signup and view all the answers

Which genes are primarily associated with Type 1 Diabetes risk due to their role in immune tolerance?

HLA DR3 and DR4 Signup and view all the answers

What is the primary cause of the absolute insulin deficit in Type 1 Diabetes?

Autoimmune destruction of beta cells Signup and view all the answers

Which of the following viral infections has been linked to the development of Type 1 Diabetes?

Coxsackie B Signup and view all the answers

What is the minimum percentage of beta cells that must be destroyed before symptoms of Type 1 Diabetes manifest?

90% Signup and view all the answers

The phenomenon where viral infections lead to the activation of autoreactive T cells is known as what?

Bystander damage Signup and view all the answers

What role does CTLA-4 play in the immune system regarding Type 1 Diabetes?

Acts as a downregulator of antigen presentation Signup and view all the answers

Which autoantigens are primarily attacked during the autoimmune response in Type 1 Diabetes?

Insulin and glutamic acid decarboxylase Signup and view all the answers

What is the significance of the twin concordance rate of 30% to 50% in Type 1 Diabetes?

Shows the influence of environmental factors Signup and view all the answers

What is the term used to describe the temporary period when remaining β-cells become hyper-productive to compensate for failing insulin response?

Honeymooning Signup and view all the answers

Which process occurs when elevated blood glucose levels lead to osmotic diuresis in the kidneys?

Increased urine production Signup and view all the answers

What is a common initial clinical manifestation of Type I diabetes mellitus associated with significant beta-cell loss?

Diabetic ketoacidosis Signup and view all the answers

What leads to the production of ketones during diabetic ketoacidosis?

Increased fatty acid release from adipose tissue Signup and view all the answers

What occurs when the remaining β-cells in diabetes become hyper-productive?

Compensation for failing insulin response Signup and view all the answers

What can occur as a consequence of rapidly declining blood pH during diabetic ketoacidosis?

Deterioration in level of consciousness Signup and view all the answers

Why might patients experience severe abdominal pain during diabetic ketoacidosis?

Increased ketone levels Signup and view all the answers

What ultimately results from an absolute insulin deficiency in Type I diabetes mellitus if left untreated?

Coma and eventual death Signup and view all the answers

Study Notes

Glucagon Synthesis and Secretion

Proglucagon yields various peptide hormones: glucagon, GLP-1, GLP-2, and others through cleavage by specific proteases.
Glucagon is primarily produced in pancreatic α cells; GLP-1 and GLP-2 are produced in neuroendocrine cells in the intestine.

Glucagon Secretion Regulators

Stimulated by:
- Decreased blood glucose levels
- Elevated serum amino acids (arginine, alanine)
- Cortisol and sympathetic nervous system activity
- Physical exercise and stress
Inhibited by:
- Increased blood glucose levels
- Somatostatin

Effects of Glucagon on the Liver

Enhances glucose production via:
- Increased glycogenolysis, reduced glycogenesis (inhibition of glucokinase and glycogen synthase, activation of glycogen phosphorylase)
- Increased gluconeogenesis, decreased glycolysis (reduced activity of key enzymes)
Promotes beta oxidation and ketosis:
- Increased beta oxidation reduces malonyl CoA levels.
- Ketogenesis is enhanced due to increased acetyl CoA from beta oxidation.
Gluconeogenic precursors (alanine, glutamate, pyruvate, lactate) are utilized more efficiently.

Diabetes Classifications

Type 1 Diabetes (T1DM):
- Onset generally in childhood, characterized by autoimmune destruction of beta cells.
- Results in absolute insulin deficiency without insulin resistance.
- Twin concordance rate is about 30-50%; linked to genetic factors such as HLA DR3/DR4.
Type 2 Diabetes (T2DM):
- Accounts for 90-95% of diabetes cases, marked by insulin resistance and inadequate insulin secretion from beta cells.

Pathogenesis of Type 1 Diabetes

Genetic Factors:
- HLA genes (DR3/DR4) contribute significantly to genetic risk.
- CTLA-4 and PTPN-22 related to immune tolerance and regulatory functions.
Environmental Factors:
- Viral infections (mumps, rubella, coxsackie B) may trigger autoimmune responses leading to beta-cell destruction.
- Mechanisms include bystander damage, molecular mimicry, and persistent viral infections.

Disease Progression and Symptoms

T1DM manifests after extensive beta cell loss (90% noted).
"Honeymoon phase" occurs when remaining beta cells temporarily compensate for insulin production.
Initial presentation often involves diabetic ketoacidosis (DKA) characterized by:
- Symptoms: polyphagia, polydipsia, polyuria, significant weight loss, dehydration.
- Ketone production from fatty acids leading to metabolic acidosis and potential loss of consciousness.

Metabolic Consequences in Diabetes

Hyperglycemia leads to osmotic diuresis, resulting in rapid fluid loss and electrolyte imbalance.
Advanced glycation end products (AGEs) affect vascular health, contributing to:
- Decreased arterial elasticity.
- Diabetic small vessel disease: includes hyaline arteriolosclerosis and diabetic microangiopathy.
- Increased capillary permeability in tissues, leading to complications such as nephropathy and retinopathy.

Diabetes Neuropathy

Neuropathy involves loss of nerve fibers, resulting in:
- Impaired pain sensation, vibration, and proprioception.
- Autonomic neuropathy leads to complications such as orthostatic hypotension and bladder dysfunction.

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Description

Explore the role of insulin in adipocytes and how glucagon synthesis is interlinked with fat metabolism. This quiz covers key concepts about proglucagon, its cleavage products, and their functions in the body. Delve into the biological mechanisms that govern fat cells and insulin's impact on energy storage.