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Questions and Answers
What is the primary physiological role of glucagon?
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?
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?
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?
How is proglucagon primarily cleaved in the pancreatic α cells?
What is the role of cortisol regarding glucagon secretion?
What is the role of cortisol regarding glucagon secretion?
In what way does glucagon affect beta-oxidation?
In what way does glucagon affect beta-oxidation?
Which metabolic pathway is primarily increased by glucagon in the liver?
Which metabolic pathway is primarily increased by glucagon in the liver?
What happens to oxaloacetate under the influence of glucagon?
What happens to oxaloacetate under the influence of glucagon?
What characterizes Type 1 diabetes in relation to pancreatic beta cells?
What characterizes Type 1 diabetes in relation to pancreatic beta cells?
Which process is inhibited by insulin to help regulate blood glucose levels?
Which process is inhibited by insulin to help regulate blood glucose levels?
What accounts for the majority of diabetes cases?
What accounts for the majority of diabetes cases?
Which of the following tissues are primarily influenced by insulin for glucose uptake?
Which of the following tissues are primarily influenced by insulin for glucose uptake?
What aspect of insulin action helps maintain a steady supply of glucose for energy?
What aspect of insulin action helps maintain a steady supply of glucose for energy?
Which of the following is NOT a factor in Type 2 diabetes development?
Which of the following is NOT a factor in Type 2 diabetes development?
What role does insulin play in cellular processes?
What role does insulin play in cellular processes?
In what situation might secondary diabetes occur?
In what situation might secondary diabetes occur?
What is a consequence of advanced glycation end products (AGEs) in the vascular system?
What is a consequence of advanced glycation end products (AGEs) in the vascular system?
What characterizes hyaline arteriolosclerosis in diabetics compared to nondiabetics?
What characterizes hyaline arteriolosclerosis in diabetics compared to nondiabetics?
Which statement about diabetic neuropathy is true?
Which statement about diabetic neuropathy is true?
What condition does diabetic microangiopathy mainly contribute to?
What condition does diabetic microangiopathy mainly contribute to?
What role does hyperglycemia have in the activation of protein kinase C pathway?
What role does hyperglycemia have in the activation of protein kinase C pathway?
Which genes are primarily associated with Type 1 Diabetes risk due to their role in immune tolerance?
Which genes are primarily associated with Type 1 Diabetes risk due to their role in immune tolerance?
What is the primary cause of the absolute insulin deficit in Type 1 Diabetes?
What is the primary cause of the absolute insulin deficit in Type 1 Diabetes?
Which of the following viral infections has been linked to the development of Type 1 Diabetes?
Which of the following viral infections has been linked to the development of Type 1 Diabetes?
What is the minimum percentage of beta cells that must be destroyed before symptoms of Type 1 Diabetes manifest?
What is the minimum percentage of beta cells that must be destroyed before symptoms of Type 1 Diabetes manifest?
The phenomenon where viral infections lead to the activation of autoreactive T cells is known as what?
The phenomenon where viral infections lead to the activation of autoreactive T cells is known as what?
What role does CTLA-4 play in the immune system regarding Type 1 Diabetes?
What role does CTLA-4 play in the immune system regarding Type 1 Diabetes?
Which autoantigens are primarily attacked during the autoimmune response in Type 1 Diabetes?
Which autoantigens are primarily attacked during the autoimmune response in Type 1 Diabetes?
What is the significance of the twin concordance rate of 30% to 50% in Type 1 Diabetes?
What is the significance of the twin concordance rate of 30% to 50% in Type 1 Diabetes?
What is the term used to describe the temporary period when remaining β-cells become hyper-productive to compensate for failing insulin response?
What is the term used to describe the temporary period when remaining β-cells become hyper-productive to compensate for failing insulin response?
Which process occurs when elevated blood glucose levels lead to osmotic diuresis in the kidneys?
Which process occurs when elevated blood glucose levels lead to osmotic diuresis in the kidneys?
What is a common initial clinical manifestation of Type I diabetes mellitus associated with significant beta-cell loss?
What is a common initial clinical manifestation of Type I diabetes mellitus associated with significant beta-cell loss?
What leads to the production of ketones during diabetic ketoacidosis?
What leads to the production of ketones during diabetic ketoacidosis?
What occurs when the remaining β-cells in diabetes become hyper-productive?
What occurs when the remaining β-cells in diabetes become hyper-productive?
What can occur as a consequence of rapidly declining blood pH during diabetic ketoacidosis?
What can occur as a consequence of rapidly declining blood pH during diabetic ketoacidosis?
Why might patients experience severe abdominal pain during diabetic ketoacidosis?
Why might patients experience severe abdominal pain during diabetic ketoacidosis?
What ultimately results from an absolute insulin deficiency in Type I diabetes mellitus if left untreated?
What ultimately results from an absolute insulin deficiency in Type I diabetes mellitus if left untreated?
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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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