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Questions and Answers
What is the location of the α subunits in the insulin receptor?
What is the location of the α subunits in the insulin receptor?
- In the nucleus
- In the mitochondria
- Extracellular (correct)
- In the cytoplasm
What is a consequence of hyperglycemia on the kidneys?
What is a consequence of hyperglycemia on the kidneys?
- Increased glucose reabsorption
- Glucose is stored in the kidneys
- Decreased glucose reabsorption (correct)
- Excretion of glucose is unaffected
What is the effect of hyperglycemia on water intake?
What is the effect of hyperglycemia on water intake?
- No effect on water intake
- Increased water intake (correct)
- Decreased water intake
- Water intake is variable
What is the purpose of measuring HbAIc concentration in diabetes?
What is the purpose of measuring HbAIc concentration in diabetes?
What happens to amino acids in the liver during diabetes?
What happens to amino acids in the liver during diabetes?
What is the effect of insulin deficiency on protein metabolism?
What is the effect of insulin deficiency on protein metabolism?
What is the initial response to glucose in terms of insulin secretion?
What is the initial response to glucose in terms of insulin secretion?
What is the role of glutamate in insulin secretion?
What is the role of glutamate in insulin secretion?
What is the effect of glucagon on glycogen in the liver?
What is the effect of glucagon on glycogen in the liver?
What is the effect of glucagon on ketone body formation?
What is the effect of glucagon on ketone body formation?
What is the role of the citric acid cycle in insulin secretion?
What is the role of the citric acid cycle in insulin secretion?
What is the feedback control of plasma glucose on insulin secretion?
What is the feedback control of plasma glucose on insulin secretion?
What is a major long-term complication of diabetes in humans?
What is a major long-term complication of diabetes in humans?
What is the role of glucokinase in glucose-stimulated insulin secretion?
What is the role of glucokinase in glucose-stimulated insulin secretion?
What is the result of ATP entering the cytoplasm in pancreatic B cells?
What is the result of ATP entering the cytoplasm in pancreatic B cells?
What is the role of GLUT-2 transporters in glucose-stimulated insulin secretion?
What is the role of GLUT-2 transporters in glucose-stimulated insulin secretion?
What is the effect of decreased lipoprotein lipase activity on lipoprotein metabolism?
What is the effect of decreased lipoprotein lipase activity on lipoprotein metabolism?
What is the response to glucose in pancreatic B cells?
What is the response to glucose in pancreatic B cells?
What term is used to describe the situation of extracellular glucose excess and intracellular glucose deficiency?
What term is used to describe the situation of extracellular glucose excess and intracellular glucose deficiency?
What is the result of accelerated atherosclerosis in diabetes?
What is the result of accelerated atherosclerosis in diabetes?
What is the effect of weight reduction on insulin resistance?
What is the effect of weight reduction on insulin resistance?
What is characterized by high circulating triglycerides and low HDL?
What is characterized by high circulating triglycerides and low HDL?
What is the result of proliferative scarring of the retina?
What is the result of proliferative scarring of the retina?
What complication of diabetes affects the autonomic nervous system and peripheral nerves?
What complication of diabetes affects the autonomic nervous system and peripheral nerves?
What is the effect of hypoglycemia on glucagon secretion?
What is the effect of hypoglycemia on glucagon secretion?
What is the mechanism of the sympathetic effect on glucagon secretion?
What is the mechanism of the sympathetic effect on glucagon secretion?
Which of the following hormones inhibits glucagon secretion?
Which of the following hormones inhibits glucagon secretion?
What is the effect of somatostatin on insulin secretion?
What is the effect of somatostatin on insulin secretion?
Which of the following stimuli increases pancreatic somatostatin secretion?
Which of the following stimuli increases pancreatic somatostatin secretion?
What is the function of pancreatic polypeptide?
What is the function of pancreatic polypeptide?
What percentage of the total cells are A cells?
What percentage of the total cells are A cells?
Where is insulin synthesized in the B cells?
Where is insulin synthesized in the B cells?
What is the half-life of insulin in the circulation in humans?
What is the half-life of insulin in the circulation in humans?
What is the effect of insulin on adipose tissue?
What is the effect of insulin on adipose tissue?
How are the contents of membrane-bound granules expelled from the cell?
How are the contents of membrane-bound granules expelled from the cell?
What is the fate of insulin after it binds to insulin receptors?
What is the fate of insulin after it binds to insulin receptors?
What is the immediate effect of Ca2+ influx on insulin secretion?
What is the immediate effect of Ca2+ influx on insulin secretion?
What is the role of glutamate in insulin secretion?
What is the role of glutamate in insulin secretion?
What is the effect of glucagon on glycogen metabolism in the liver?
What is the effect of glucagon on glycogen metabolism in the liver?
What is the effect of glucagon on ketone body formation in the liver?
What is the effect of glucagon on ketone body formation in the liver?
What is the feedback control mechanism of plasma glucose on insulin secretion?
What is the feedback control mechanism of plasma glucose on insulin secretion?
What is the effect of glucagon on lipolysis?
What is the effect of glucagon on lipolysis?
What is the primary effect of glucagon on lipid metabolism?
What is the primary effect of glucagon on lipid metabolism?
What is the role of β-adrenergic receptors in the regulation of glucagon secretion?
What is the role of β-adrenergic receptors in the regulation of glucagon secretion?
Which of the following hormones has a paracrine effect on the pancreatic islets?
Which of the following hormones has a paracrine effect on the pancreatic islets?
What is the effect of cholecystokinin on glucagon secretion?
What is the effect of cholecystokinin on glucagon secretion?
What is the effect of somatostatin 28 on insulin secretion?
What is the effect of somatostatin 28 on insulin secretion?
What is the relationship between pancreatic polypeptide and other amino acid polypeptides?
What is the relationship between pancreatic polypeptide and other amino acid polypeptides?
What is the primary effect of pancreatic polypeptide on digestion in humans?
What is the primary effect of pancreatic polypeptide on digestion in humans?
What is the typical pattern of plasma glucose levels seen in functional hypoglycemia?
What is the typical pattern of plasma glucose levels seen in functional hypoglycemia?
What is the primary cause of polyuria in diabetes mellitus?
What is the primary cause of polyuria in diabetes mellitus?
What is the effect of fasting on the secretion of pancreatic polypeptide?
What is the effect of fasting on the secretion of pancreatic polypeptide?
What is the typical outcome of chronic mild hypoglycemia in individuals?
What is the typical outcome of chronic mild hypoglycemia in individuals?
What are the two fundamental defects that contribute to the abnormalities seen in diabetes mellitus?
What are the two fundamental defects that contribute to the abnormalities seen in diabetes mellitus?
In muscle cells, what is the primary mechanism by which insulin stimulates glucose entry?
In muscle cells, what is the primary mechanism by which insulin stimulates glucose entry?
What is the primary difference in how insulin stimulates glucose entry in muscle and liver cells?
What is the primary difference in how insulin stimulates glucose entry in muscle and liver cells?
What is the structure of the insulin receptor?
What is the structure of the insulin receptor?
In what tissues does insulin stimulate glucose entry by increasing the number of GLUTs?
In what tissues does insulin stimulate glucose entry by increasing the number of GLUTs?
What is the effect of insulin on ketone body formation in the liver?
What is the effect of insulin on ketone body formation in the liver?
What is the effect of insulin on protein catabolism and gluconeogenic amino acid release in muscle cells?
What is the effect of insulin on protein catabolism and gluconeogenic amino acid release in muscle cells?
What is the effect of insulin on glucose entry into muscle cells?
What is the effect of insulin on glucose entry into muscle cells?
What is the function of glucokinase in the liver?
What is the function of glucokinase in the liver?
What is the structure of the insulin receptor?
What is the structure of the insulin receptor?
What is the effect of insulin on ketone body formation in the liver?
What is the effect of insulin on ketone body formation in the liver?
What is the effect of insulin on protein synthesis in muscle?
What is the effect of insulin on protein synthesis in muscle?
What is the mode of glucose transport into intestinal and kidney cells?
What is the mode of glucose transport into intestinal and kidney cells?
What is the effect of glucagon on glycogen in the liver?
What is the effect of glucagon on glycogen in the liver?
What is the role of glutamate in insulin secretion?
What is the role of glutamate in insulin secretion?
What is the effect of Ca2+ influx on insulin secretion?
What is the effect of Ca2+ influx on insulin secretion?
What is the effect of glucagon on gluconeogenesis in the liver?
What is the effect of glucagon on gluconeogenesis in the liver?
What is the effect of glucagon on ketone body formation in the liver?
What is the effect of glucagon on ketone body formation in the liver?
What is a consequence of insulin deficiency in animals?
What is a consequence of insulin deficiency in animals?
What is the feedback control mechanism of plasma glucose on insulin secretion?
What is the feedback control mechanism of plasma glucose on insulin secretion?
What is the effect of hyperglycemia on blood?
What is the effect of hyperglycemia on blood?
What is the fate of glucose molecules in the kidneys during hyperglycemia?
What is the fate of glucose molecules in the kidneys during hyperglycemia?
What is the result of episodic plasma glucose elevation over time?
What is the result of episodic plasma glucose elevation over time?
What happens to amino acids in diabetes?
What happens to amino acids in diabetes?
What is the effect of insulin deficiency on glucose metabolism?
What is the effect of insulin deficiency on glucose metabolism?
What is the effect of insulin deficiency on the blood amino acid level?
What is the effect of insulin deficiency on the blood amino acid level?
What is the result of decreased removal of triglycerides into the fat depots in uncontrolled diabetes?
What is the result of decreased removal of triglycerides into the fat depots in uncontrolled diabetes?
What is the effect of adrenal glucocorticoids on gluconeogenesis in severely ill diabetics?
What is the effect of adrenal glucocorticoids on gluconeogenesis in severely ill diabetics?
What is the reason for the increased formation of ketone bodies in diabetes?
What is the reason for the increased formation of ketone bodies in diabetes?
What is the effect of insulin on the hormone-sensitive lipase in adipose tissue?
What is the effect of insulin on the hormone-sensitive lipase in adipose tissue?
What is the relationship between the plasma level of free fatty acids and the plasma glucose level in diabetes?
What is the relationship between the plasma level of free fatty acids and the plasma glucose level in diabetes?
What is a consequence of intracellular glucose deficiency in many cells?
What is a consequence of intracellular glucose deficiency in many cells?
What is a long-term complication of diabetes?
What is a long-term complication of diabetes?
What is associated with obesity and relates to insulin resistance?
What is associated with obesity and relates to insulin resistance?
What is the result of proliferative scarring of the retina in diabetic retinopathy?
What is the result of proliferative scarring of the retina in diabetic retinopathy?
What is characterized by high circulating triglycerides and low HDL?
What is characterized by high circulating triglycerides and low HDL?
What is affected by the neuropathic abnormalities in diabetes?
What is affected by the neuropathic abnormalities in diabetes?
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Study Notes
Diabetes and Insulin Regulation
- Insulin deficiency leads to a situation where there is an extracellular glucose excess and an intracellular glucose deficiency, known as "starvation in the midst of plenty".
- Diabetes is complicated by acidosis and coma, and long-standing diabetes leads to microvascular, macrovascular, and neuropathic disease.
- Microvascular abnormalities include proliferative scarring of the retina (diabetic retinopathy) and renal disease (diabetic nephropathy), leading to blindness and chronic kidney disease.
- Macrovascular abnormalities are due to accelerated atherosclerosis, leading to increased incidence of stroke and myocardial infarction.
- Neuropathic abnormalities involve the autonomic nervous system and peripheral nerves.
Obesity and Insulin Resistance
- Obesity is increasing in incidence and relates to the regulation of food intake and energy balance.
- As body weight increases, insulin resistance increases, decreasing insulin's ability to move glucose into fat and muscle cells.
- Weight reduction decreases insulin resistance.
- Associated with obesity are hyperinsulinemia, dyslipidemia, and accelerated development of atherosclerosis.
Regulation of Insulin Secretion
- Glucose acts directly on pancreatic B cells to increase insulin secretion.
- The response to glucose is biphasic, with a rapid but short-lived increase in secretion followed by a prolonged increase.
- Glucose enters B cells via GLUT-2 transporters and is phosphorylated by glucokinase, then metabolized to pyruvate in the cytoplasm.
- Pyruvate enters the mitochondria and is metabolized to CO2 and H2O via the citric acid cycle, with the formation of ATP by oxidative phosphorylation.
Glucagon Regulation
- Glucagon is produced by the A cells of pancreatic islets and the upper gastrointestinal tract.
- Glucagon is glycogenolytic, gluconeogenic, lipolytic, and ketogenic.
- In the liver, glucagon increases breakdown of glycogen and plasma glucose, increases gluconeogenesis, and elevates the metabolic rate.
- Glucagon secretion is increased by hypoglycemia, stimulation of the sympathetic nerves, protein meal, and infusion of various amino acids.
Insulin and Glucagon Interaction
- Insulin and glucagon have opposing effects on glucose metabolism.
- Insulin increases glucose entry into cells, glycogen synthesis, and protein synthesis, while decreasing glucose output from the liver.
- Glucagon increases glucose output from the liver, glycogenolysis, and gluconeogenesis.
Other Islet Cell Hormones
- Somatostatin is produced by D cells of pancreatic islets and inhibits the secretion of insulin, glucagon, and pancreatic polypeptide.
- Pancreatic polypeptide is produced by F cells of pancreatic islets and slows the absorption of food in humans.
- Its secretion is increased by a meal containing protein and fasting, exercise, and acute hypoglycemia.### Insulin Receptor Structure
- α subunits of the insulin receptor are extracellular and bind insulin
- β subunits of the insulin receptor span the membrane
Consequences of Insulin Deficiency
- Insulin deficiency is a common pathologic condition in humans
- Can be produced in animals by pancreatectomy, certain toxins, drugs that inhibit insulin secretion, or anti-insulin antibodies
Effects of Hyperglycemia
- Hyperglycemia causes symptoms due to hyperosmolality of the blood
- Leads to glycosuria as the renal capacity for glucose reabsorption is exceeded
- Results in osmotic diuresis, dehydration, and polydipsia
- Leads to non-enzymatic glycation of hemoglobin A, forming HbAIc, which is a clinical index of diabetic control
Effects of Hyperglycemia on Protein Metabolism
- Increases the rate of amino acid catabolism to CO2 and H2O
- Increases conversion of amino acids to glucose in the liver (gluconeogenesis)
- Adrenal glucocorticoids contribute to increased gluconeogenesis in severely ill diabetics
- Decreased protein synthesis in muscle leads to increased blood amino acid levels
Fat Metabolism in Diabetes
- Accelerated lipid catabolism and increased ketone body formation
- Decreased synthesis of fatty acids and triglycerides
- Decreased conversion of glucose to fatty acids in adipose tissue due to intracellular glucose deficiency
- Insulin's inhibition of hormone-sensitive lipase is absent, leading to increased plasma free fatty acid levels
- Plasma triglyceride and chylomicron levels, as well as FFA, are increased in uncontrolled diabetes, often resulting in a lipemic plasma
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