90 Questions
What is the location of the α subunits in the insulin receptor?
Extracellular
What is a consequence of hyperglycemia on the kidneys?
Decreased glucose reabsorption
What is the effect of hyperglycemia on water intake?
Increased water intake
What is the purpose of measuring HbAIc concentration in diabetes?
As an integrated index of diabetic control
What happens to amino acids in the liver during diabetes?
They are converted to glucose
What is the effect of insulin deficiency on protein metabolism?
Increased protein catabolism
What is the initial response to glucose in terms of insulin secretion?
Initial spike of insulin secretion
What is the role of glutamate in insulin secretion?
It commits a second pool of secretory granules to the releasable form
What is the effect of glucagon on glycogen in the liver?
It increases glycogen breakdown
What is the effect of glucagon on ketone body formation?
It increases ketone body formation
What is the role of the citric acid cycle in insulin secretion?
It increases glutamate production
What is the feedback control of plasma glucose on insulin secretion?
It is a feedback loop with great precision
What is a major long-term complication of diabetes in humans?
Atherosclerotic vascular disease
What is the role of glucokinase in glucose-stimulated insulin secretion?
It phosphorylates glucose to pyruvate
What is the result of ATP entering the cytoplasm in pancreatic B cells?
Inhibition of ATP-sensitive K+ channels
What is the role of GLUT-2 transporters in glucose-stimulated insulin secretion?
They transport glucose into the B cell
What is the effect of decreased lipoprotein lipase activity on lipoprotein metabolism?
Decreased removal of VLDL and LDL from the circulation
What is the response to glucose in pancreatic B cells?
A biphasic increase in insulin secretion
What term is used to describe the situation of extracellular glucose excess and intracellular glucose deficiency?
Starvation in the midst of plenty
What is the result of accelerated atherosclerosis in diabetes?
Increased incidence of stroke and myocardial infarction
What is the effect of weight reduction on insulin resistance?
Decreases insulin resistance
What is characterized by high circulating triglycerides and low HDL?
Dyslipidemia
What is the result of proliferative scarring of the retina?
Blindness
What complication of diabetes affects the autonomic nervous system and peripheral nerves?
Diabetic neuropathy
What is the effect of hypoglycemia on glucagon secretion?
It increases glucagon secretion
What is the mechanism of the sympathetic effect on glucagon secretion?
Via β-adrenergic receptors and cAMP
Which of the following hormones inhibits glucagon secretion?
Secretin
What is the effect of somatostatin on insulin secretion?
It inhibits insulin secretion
Which of the following stimuli increases pancreatic somatostatin secretion?
Glucose and amino acids
What is the function of pancreatic polypeptide?
It is closely related to neuropeptide Y
What percentage of the total cells are A cells?
20%
Where is insulin synthesized in the B cells?
Rough endoplasmic reticulum
What is the half-life of insulin in the circulation in humans?
5 min
What is the effect of insulin on adipose tissue?
Increase glucose entry
How are the contents of membrane-bound granules expelled from the cell?
Exocytosis
What is the fate of insulin after it binds to insulin receptors?
It is destroyed by proteases in the endosomes
What is the immediate effect of Ca2+ influx on insulin secretion?
Exocytosis of readily releasable pool of insulin-containing secretory granules
What is the role of glutamate in insulin secretion?
Commits secretory granules to the releasable form
What is the effect of glucagon on glycogen metabolism in the liver?
Increases glycogen breakdown
What is the effect of glucagon on ketone body formation in the liver?
Increases ketone body formation
What is the feedback control mechanism of plasma glucose on insulin secretion?
Negative feedback
What is the effect of glucagon on lipolysis?
Increases lipolysis
What is the primary effect of glucagon on lipid metabolism?
Increased ketogenesis
What is the role of β-adrenergic receptors in the regulation of glucagon secretion?
Mediation of the sympathetic effect on glucagon secretion
Which of the following hormones has a paracrine effect on the pancreatic islets?
Somatostatin
What is the effect of cholecystokinin on glucagon secretion?
Increase in glucagon secretion
What is the effect of somatostatin 28 on insulin secretion?
Inhibition of insulin secretion
What is the relationship between pancreatic polypeptide and other amino acid polypeptides?
It is closely related to polypeptide YY and neuropeptide Y
What is the primary effect of pancreatic polypeptide on digestion in humans?
It slows the absorption of food
What is the typical pattern of plasma glucose levels seen in functional hypoglycemia?
A normal rise followed by a subsequent fall to hypoglycemic levels
What is the primary cause of polyuria in diabetes mellitus?
Increased glucose levels in the blood
What is the effect of fasting on the secretion of pancreatic polypeptide?
It increases the secretion of pancreatic polypeptide
What is the typical outcome of chronic mild hypoglycemia in individuals?
Incoordination and slurred speech
What are the two fundamental defects that contribute to the abnormalities seen in diabetes mellitus?
Reduced glucose entry into peripheral tissues and increased glucose liberation from the liver
In muscle cells, what is the primary mechanism by which insulin stimulates glucose entry?
Increasing the number of glucose transporters in the cell membrane
What is the primary difference in how insulin stimulates glucose entry in muscle and liver cells?
Insulin increases GLUTs in muscle cells but induces glucokinase in liver cells
What is the structure of the insulin receptor?
A tetramer made up of two α and two β glycoprotein subunits
In what tissues does insulin stimulate glucose entry by increasing the number of GLUTs?
Muscle, adipose, and some other tissues
What is the effect of insulin on ketone body formation in the liver?
It decreases ketone body formation
What is the effect of insulin on protein catabolism and gluconeogenic amino acid release in muscle cells?
It decreases protein catabolism and gluconeogenic amino acid release
What is the effect of insulin on glucose entry into muscle cells?
Increases the number of glucose transporters in the cell membranes
What is the function of glucokinase in the liver?
Phosphorylates glucose, increasing its entry into the cell
What is the structure of the insulin receptor?
A tetramer made up of two α and two β subunits
What is the effect of insulin on ketone body formation in the liver?
Decreases ketone body formation
What is the effect of insulin on protein synthesis in muscle?
Increases protein synthesis
What is the mode of glucose transport into intestinal and kidney cells?
Both facilitated diffusion and active transport with Na+
What is the effect of glucagon on glycogen in the liver?
Breakdown of glycogen
What is the role of glutamate in insulin secretion?
Stimulates release of insulin
What is the effect of Ca2+ influx on insulin secretion?
Stimulates release of insulin
What is the effect of glucagon on gluconeogenesis in the liver?
Stimulates gluconeogenesis
What is the effect of glucagon on ketone body formation in the liver?
Increases ketone body formation
What is a consequence of insulin deficiency in animals?
Selective destruction of the B cells of the pancreatic islets
What is the feedback control mechanism of plasma glucose on insulin secretion?
Negative feedback control
What is the effect of hyperglycemia on blood?
Hyperosmolality
What is the fate of glucose molecules in the kidneys during hyperglycemia?
They are excreted in the urine
What is the result of episodic plasma glucose elevation over time?
Formation of HbAIc
What happens to amino acids in diabetes?
They are catabolized to CO2 and H2O at an increased rate
What is the effect of insulin deficiency on glucose metabolism?
Increased glucose concentration in the blood
What is the effect of insulin deficiency on the blood amino acid level?
It increases
What is the result of decreased removal of triglycerides into the fat depots in uncontrolled diabetes?
Increased plasma triglyceride levels
What is the effect of adrenal glucocorticoids on gluconeogenesis in severely ill diabetics?
They increase gluconeogenesis
What is the reason for the increased formation of ketone bodies in diabetes?
Accelerated lipid catabolism
What is the effect of insulin on the hormone-sensitive lipase in adipose tissue?
It inhibits the lipase
What is the relationship between the plasma level of free fatty acids and the plasma glucose level in diabetes?
The FFA level is directly proportional to the plasma glucose level
What is a consequence of intracellular glucose deficiency in many cells?
Starvation in the midst of plenty
What is a long-term complication of diabetes?
All of the above
What is associated with obesity and relates to insulin resistance?
All of the above
What is the result of proliferative scarring of the retina in diabetic retinopathy?
Blindness
What is characterized by high circulating triglycerides and low HDL?
Dyslipidemia
What is affected by the neuropathic abnormalities in diabetes?
Autonomic nervous system and peripheral nerves
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
Test your knowledge of insulin's structure, functions, and the consequences of its deficiency in humans and animals. Learn about the α and β subunits, insulin secretion, and its effects on the body.
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