Question 1 (10 points) Top of

Question 1 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to normal response to the carbohydrate meal: 1. What are the three metabolic pathways by which a rise in plasma insulin leads to a fall in plasma glucose? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)

ATP production, amino acid synthesis, triglyceride synthesis. (not glycogenesis)

Insulin facilitates the removal of glucose from plasma by enhancing membrane transport of glucose. Glycogen synthesis, primarily in skeletal muscle, is enhanced due to increased activity of glycogen synthetase. Lipogenesis in liver and adipose tissue is enhanced by increased activity of several enzymes and depressed activity of several others. In addition, oxidation of glucose is enhanced in most cells by insulin (Tepperman, p. 172; Guyton, pp. 915-917; Ganong, pp. 256-257).
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Question 2 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to normal response to the carbohydrate meal: 2. What are at least four controllers of insulin release? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)

High blood glucose levels, Acetylcholine, arginine, leucine, glucose-dependent insulinotropic peptide (GIP)

Insulin secretion is enhanced by increased plasma glucose acting directly on the beta-cell, secretin, gastrin and cholecystokinin, glucagon, vagal stimulation, increased plasma amino acids glucose secretin gastrin cholecystokinin amino acids
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Question 3 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to normal response to the carbohydrate meal: 3. At 240 minutes, plasma insulin concentration of the normal person is several times the control level, but the plasma glucose concentration is only slightly elevated. What balances the tendency for insulin to decrease the plasma glucose concentration? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)

The tendency for insulin to decrease the plasma glucose concentration is due to the ability of glucose to accelerate facilitated diffusion of glucose into cells. Both the negative feedback action of low glucose concentrations on insulin and the positive effect of glucogon on glucose levels serve to compensate the effects of insulin.
Growth hormone is known to increase in response to a decrease in plasma glucose. This hormone acts synergistically with insulin to promote protein synthesis, but antagonizes the effect of insulin on plasma glucose. It has been proposed that after a mixed meal, first insulin is secreted and glucose is cleared from plasma. Then, growth hormone and glucagon antagonize this effect of insulin but act synergistically to increase protein synthesis. Then, as insulin returns to fasting levels, glucagon and growth hormone promote fat mobilization with sparing of glucose and protein (Tepperman, pp. 48, 172; Ganong, p. 261; Guyton, p. 922).
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Question 4 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to normal response to the carbohydrate meal: 4. What is the normal stimulus for glucagon release? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)

Hypoglycemia

Glucagon is released by cholecystokinin and in response to an increased plasma amino acid synthesis concentration and a decreased plasma glucose concentration (Tepperman, p. 182; Ganong, p. 260; Guyton, p. 922).
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Question 5 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to the normal response to the protein meal: 5. What is the most likely stimulus for insulin release with this meal? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)

A rise in blood amino acids argentine and leucine, in addition to a pre-existing state of hypoglycemia.

Since plasma glucose concentration is increased negligibly, the increased glucagon and amino acid levels are primarily responsible for the release of insulin. Glucagon and the gastrointestinal hormones may also contribute (Tepperman, p. 182; Ganong, pp. 257-258). glucagon amino acids
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Question 6 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to the normal response to the protein meal: 6. Why does the plasma glucose concentration fail to fall in the presence of the elevated insulin concentration? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)

A rise in amino acids also stimulates glucagons secretion.

The dramatic rise in glucagon counteracts the action of insulin on plasma glucose by promoting glycogenolysis and gluconeogenesis. The increased glycogenolysis and gluconeogenesis may both be a result of the elevation of intracellular cyclic AMP by glucagon. The secretion of growth hormone is also stimulated by a protein meal and has a powerful anti-insulin effect (Ganong, pp. 260-261; Guyton, pp. 927, 928).

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Question 7 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to the normal response to the protein meal: 7. What coordinated action of insulin, glucagon, and growth hormone could be occurring under these circumstances? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)

Insulin secretion would increase in response to amino acids arginine and leucine to decrease blood glucose levels. Glucagon secretion would increase in response to elevated amino acid concentration. Growth hormone would stimulate secretion of insulin because it acts to elevate blood glucose.

Insulin both decreases plasma glucose and increases protein synthesis. Glucagon counteracts the effect of insulin on plasma glucose allowing the effect of insulin on protein synthesis to continue. Growth hormone antagonizes insulin’s action on plasma glucose, and more importantly promotes protein synthesis. Insulin and growth hormone act synergistically to increase protein synthesis (Teppermafl, pp. 37, 158-159).
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Question 8 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to the normal response to the protein meal: 8. How is insulin removed from the plasma? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)
The negative feedback action of low blood glucose levels ingibits release of insulin, and the remaining insulin in circulation would be metabolized by the cells of the body as it facilitates glucose diffusion.
Insulin is destroyed by the liver which initially splits the disulphide bonds (Tepperman, p. 177; Ganong, p. 248).
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Question 9 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to the diabetic patient: 9. Can the hyperglycemia of the diabetic patient be explained solely in terms of insulin lack? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)

The hyperglycemia of the diabetic patient can also be explained by increased production of glucose by uninhibited glucagon.
Since the fasting insulin level is slightly higher in the diabetic patient in both Figures 11 and 12, and since the insulin concentration in response to the high protein meal is higher in diabetic than the normal, it is difficult to explain the elevated plasma glucose solely on the basis of insulin lack. On the other hand, the insulin response to the carbohydrate meal was far less for the diabetic than the normal. Therefore, in this patient the hyperglycemia seems to be the result of both insulin lack and resistance of some tissues to the effect of insulin. In other words, diabetes is probably in many cases a disease of relative insulin insufficiency (Tepperman, pp. 181-182).

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Question 10 (10 points)
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Below are the results of an experiment in which (1) a large carbohydrate and (2) a large protein meal were given to a normal person and to a person with diabetes mellitus. Plasma insulin, glucagon and glucose concentrations were measured (Figs. 11 and 12). Questions: With regard to the diabetic patient: 10. What might the failure of glucagon to decrease with the carbohydrate meal do to the clearance of the extra glucose from the blood? What would happen to hepatic glucose turnover? Fig. 11 (left) .–Results of experiment in which a large carbohydrate meal was given to a normal and to a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.) Fig. 12 (right) .–Results of experiment in which a large protein meal was given to a normal and a diabetic person. (From Muller, W. A., et al.: Abnormal alpha-cell function in diabetes, New England J. Med. 283:110, 1970.)
The failure of glucagons to decrease with the carbohydrate meal would inhibit the clearance of extra glucose from the blood. Hepatic glucose turnover would serve to convert excess glucose into glycogen and triglycerides.

Since glucagon, via cyclic AMP, enhances glycogenolysis and gluconeogenesis, the lowering of plasma glucose concentration and stimulation of glycogen synthesis by insulin would be counteracted to some extent. Thus, hepatic glucose turnover would increase but plasma glucose concentration would not necessarily change.
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