Chp 26: Insulin/Glucagon

Question 1

1. Why is insulin called the anabolic hormone?

Answer 1

• Anabolic refers to making large molecules from smaller ones. It promotes fuel storage, the building of the structural components of the cell, and the synthesis of enzymes, all from smaller molecules
• Insulin is a builder – it regulates the building up (synthesis) of molecules while simultaneously inhibiting the breakdown of molecules by hormones like glucagon, epinephrine, and other stress hormones we don’t’ cover in this class
• Insulin also promotes the uptake and catabolism of glucose, and this may be considered catabolism. However this is also the pathway for fatty acid synthesis and provides energy for anabolic reactions. So insulin promotes storage, synthesis, and use of fuels for growth
• An anabolic pathway builds bigger molecules out of smaller ones. For example, glycogen from glucose, amino acids from TCA cycle intermediates, gluconeogenesis, fatty acid synthesis, and protein synthesis

Question 2

2. Which counterregulatory hormones are mentioned in this chapter and why are they called counterregulatory hormones?

Answer 2

• Glucagon, epinephrine, norepinephrine, and cortisol are the counterregulatory hormones covered in this chapter. They are referred to as such because they act in opposition to insulin, the historic “regulatory hormone”
• Glucagon, epinephrine, and norepinephrine stimulate glycogenolysis, proteolysis, and fatty acid mobilization and catabolism. These 3 plus cortisol also stimulate gluconeogenesis, which one could argue is anabolism – but it is “counter” to insulin
• Low blood glucose promotes stress on the body, sending neuronal signals that release counterregulatory hormones

Question 3

3. Which hormones are exerting a major effect upon fuel metabolism following a meal?

Answer 3

High insulin

(An increase in counterregulatory hormones does not always means a decrease in insulin. Following a high protein meal, glucagon and insulin both rise.)

Question 4

3. Which hormones are exerting a major effect upon fuel metabolism after an overnight fast?

Answer 4

High glucagon, cortisol, and epinephrine

Other info: The degree to which counterregulatory hormone is increased during fasting, stress, and exercise varies but they all increase. That is, glucagon rises much more than epinephrine and cortisol after an overnight fast, but they all increase. Likewise, epinephrine would increase much more than glucagon and cortisol during exercise; but again, they would all increase

Question 5

3. Which hormones are exerting a major effect upon fuel metabolism during stress?

Answer 5

Epinephrine, cortisol, and glucagon all rise

Other info: Epinephrine would increase much more than glucagon and cortisol during exercise; but again, they would all increase.

Question 6

4. What is the effect of insulin upon the storage of glucose in glycogen?

Answer 6

Insulin increases the rate of the pathway for converting glucose to glycogen (glycogen synthesis is another example of anabolism)

Question 7

4. What is the effect of insulin upon the mobilization of glucose from glycogen?

Answer 7

Insulin inhibits glycogenolysis (insulin is an anabolic hormone. Glycogenolysis is an example of catabolism)

Question 8

4. What is the effect of insulin upon the synthesis of fatty acids from glucose in the liver?

Answer 8

Insulin activates the rate of the pathway of fatty acid synthesis from glucose (anabolism)

Question 9

4. What is the effect of insulin upon the synthesis of triacylglycerols in liver and adipose tissue?

Answer 9

Insulin increases the rate of the pathway of the synthesis of triacylglycerols in liver and adipose tissue (anabolism)

Question 10

4. What is the effect of insulin upon mobilization of free fatty acids from adipose tissue?

Answer 10

Insulin inhibits the mobilization (breakdown) of free fatty acids from adipose tissue (catabolism)

Question 11

4. What is the effect of insulin upon the synthesis of proteins in most tissues?

Answer 11

Insulin increases the rate of protein synthesis in most tissues (anabolism)

Question 12

4. What is the effect of insulin upon the mobilization of amino acids from proteins for gluconeogenesis?

Answer 12

Insulin inhibits the hydrolysis of proteins (proteolysis) and the mobilization of amino acids for gluconeogenesis (catabolism)

Question 13

5. What effect does a high carbohydrate meal have on insulin?

Answer 13

Insulin will rise following a high carbohydrate meal. The major signal for insulin secretion is the concentration of glucose. So as glucose rises, so does insulin

Question 14

5. What effect does an overnight fast have on insulin?

Answer 14

Insulin will fall in concentration after an overnight fast. Again, the major signal for insulin secretion is the concentration of glucose. Glucose is usually back to normal within two hours following a meal so it would certainly be low after an overnight fast

Question 15

5. What effect does stress have on insulin?

Answer 15

During times of stress, the insulin concentration is low. Increased epinephrine inhibits insulin release

Question 16

6. What is the effect of glucagon upon the following metabolic pathways?

Answer 16

• The storage of glucose in glycogen: Glucagon inhibits the storage of glucose in glycogen (glycogen synthesis is anabolic)
• The mobilization of glucose from glycogen: Glucagon increases the rate of glycogenolysis (catabolic)
• The synthesis of fatty acids from glucose in the liver: Glucagon inhibits the synthesis of fatty acids from glucose in the liver (anabolic)
• The synthesis of triacylglycerols in liver and adipose tissue: Glucagon inhibits the synthesis of triacylglycerols in liver and adipose tissue (anabolic)
• The mobilization of free fatty acids from adipose tissue: Glucagon increases the mobilization of free fatty acids from lipids in adipose tissue (catabolic)
• The mobilization of amino acids from muscle proteins for gluconeogenesis: Glucagon increases the rate of amino acid mobilization from proteins for gluconeogenesis. However, in the skeletal muscle there is no direct effect because skeletal muscles lack glucagon receptors. The indirect effect is that glucagon lowers the concentration of amino acids by stimulating gluconeogenesis, and the lower amino acid concentrations favor the catabolism of proteins in skeletal muscle (catabolic)

Question 17

7. What effect would a high carbohydrate meal have on glucagon?

Answer 17

Glucagon concentration will be low following a high carbohydrate meal because high glucose will increase insulin secretion and insulin will inhibit glucagon release

Question 18

7. What effect would an overnight fast have on glucagon?

Answer 18

Glucagon levels will be high after an overnight fast because low insulin levels will allow secretion from the alpha-cells. Insulin will be low because glucose is low

Question 19

7. What effect would stress have on glucagon?

Answer 19

Glucagon is high in times of stress. The stress hormones tend to rise/fall together

Question 20

8. What is the effect of stress hormones as a group upon the storage of glucose in glycogen?

Answer 20

Inhibition

Question 21

8. What is the effect of stress hormones as a group upon the mobilization of glucose from glycogen?

Answer 21

Activation

Question 22

8. What is the effect of stress hormones as a group upon the synthesis of fatty acids from glucose in the liver?

Answer 22

Inhibition

Question 23

8. What is the effect of stress hormones as a group upon the synthesis of triacylglycerols in liver and adipose tissue?

Answer 23

Inhibition

Question 24

8. What is the effect of stress hormones as a group upon the mobilization of free fatty acids from adipose tissue?

Answer 24

Activation

Question 25

8. What is the effect of stress hormones as a group upon the synthesis of proteins in most tissues?

Answer 25

Inhibition

Question 26

8. What is the effect of stress hormones as a group upon the mobilization of amino acids from proteins for gluconeogenesis?

Answer 26

Activation

Question 27

8. How is cortisol acting alone different from cortisol with the other stress hormones present?

Answer 27

The role of cortisol is confusing is cortisol is considered alone without glucagon and epinephrine. Cortisol seems to activate both glycogen synthesis and glycogenolysis. However, when all 3 stress hormones are present, the result is clear: glycogenolysis is activated and glycogen synthesis are inhibited

Question 28

9. What are the important events in the synthesis of insulin from synthesis of the preprohormone to precipitation in storage granules?

Answer 28

(Fig 26.10)

• The synthesis of insulin takes place in the beta cell of the endocrine pancreas, located within clusters of glands calls the islets of Langerhans. The amino acid sequence is translated on the rough endoplasmic reticulum as a preprohormone. The “pre” sequence (a short sequence at the N terminal end) is necessary for the entrance of preproinsulin into the lumen of the rough ER. Once inside the lumen, the “pre” sequence is cleaved from the proinsulin. The proinsulin folds into a conformation stabilized by interchain disulfide bonds
• Proinsulin is transported to the Golgi where the C-peptide and several amino acids are hydrolyzed (cleaved) proteolytic enzymes (proteases). This cleavage produces insulin from proinsulin. Insulin now consists of two chains, the A chain and the B chain held together by two interchain disulfide bonds. The intra chain disulfide bonds became interchain disulfide bonds when insulin was cleaved into two polypeptide chains. Insulin molecules form a precipitate with zinc, and small portions of the Golgi are squeezed off as insulin storage vesicles (granules)
• When the granule is secreted, the insulin-zinc precipitate dissolves and both insulin & C-peptide are released into the intracellular space and blood. Insulin is eventually destroyed by insulinase in the liver

Question 29

10. Describe the mechanism of release of insulin from beta cells in response to increased blood glucose.

Answer 29

• When blood glucose rises, increases amounts of glucose enters the B-cells of the pancreas via the glucose transporters. Glucokinase then phosphorylates the glucose and allows it go through glycolysis and TCA cycle, thereby creating more ATP and increasing the ATP concentration in the B-cell. Increasing ATP concentration causes the inhibition of ATP sensitive K⁺ channels
• Because the Na⁺/K⁺ ATPase pumps in cells keep the K⁺ concentration insie the cell much higher than that of outside the cell, K⁺ from moving out of the cell (down its gradient). It stops K⁺ leakage from maintaining membrane polarization and causes membrane depolarization, meaning that the membrane potential is now more positive. This voltage change across the membrane activates voltage gated Ca²⁺ channels, allowing Ca²⁺ to enter the cell. This increasing Ca²⁺ concentration causes exocytotic vesicles to fuse with the plasma membrane and release their contents of insulin into the intercellular space and the bloodstream

Question 30

11. Explain how a mutation that caused an elevated Km for glucokinase could explain some types of MODY.

Answer 30

• In the range between 80 mg/dL to 300 mg/dL, the rate of insulin release is dependent upon the rate of glycolysis. In beta-cells, the rate of glycolysis controls the rate at which glucose is fully oxidized and the rate of ATP synthesis by oxidative phosphorylation. Thus, beta-cell glycolysis is responsible for maintaining a particular ATP/ADP concentration
• If the K_M for a patient with MODY is higher than a normal person, their glucose concentration will have to be higher than the normal person to achieve the same rate of conversion of glucose → glucose 6-P and rate of glycolysis. In other words, the pt with MODY will convert less glucose to glucose 6-P than a normal person, given the same level of blood and cellular glucose. If they convert less glucose, they will produce less ATP and their ATP/ADP&AMP ratio will be lower
• As a result, they will inhibit the K⁺ channel to a lesser extent, have less depolarization, and release less glucose. That is, given the same level of blood glucose, the MODY pt will always produce less insulin. As a result, a pt with MODY will always have a higher blood glucose

Other notes: There are many causes of MODY and this only one of them. Rate of insulin release is proportionate to glucose concentration between 80 and 300 mg/dL. At 300 mg/dL, insulin release is at its maximum. Under normal circumstances, the threshold for insulin release is approximately 80 mg/dL. Below this level there tends to be an “all or nothing” response. However, above 80 mg/dL and up to 300 mg/dL, the rate of insulin release is proportional to the concentration of available circulating blood glucose

Question 31

12. What is the effect of a high carbohydrate meal upon insulin release and what is the hormone or metabolite directly affecting the B-cells?

Answer 31

Increased insulin release in response to increased glucose (metabolite)

Question 32

12. What is the effect of a high protein meal upon insulin release and what is the hormone or metabolite directly affecting the B-cells?

Answer 32

Increased insulin release in response to increased amino acids (metabolite). Much lower response than with glucose

Question 33

12. What is the effect of starvation, trauma, or vigorous exercise upon insulin release and what is the hormone or metabolite directly affecting the B-cells?

Answer 33

Decreased insulin release in response to epinephrine (hormone). Epinephrine binds to receptors on the beta cells.

Note! The release of glucagon has very little direct effect upon beta cells and insulin release

Question 34

13. What is the effect of a high carbohydrate meal upon glucagon release and what is the hormone or metabolite directly affecting the a-cells?

Answer 34

Decreased glucagon release in response to increased insulin (hormone) in response to increased glucose (metabolite). Insulin binds to receptors on alpha cells immediately after release so the concentration of insulin is very high. The blood flow is from beta cells to alpha cells, not the other way around

Question 35

13. What is the effect of a high protein meal upon glucagon release and what is the hormone or metabolite directly affecting the a-cells?

Answer 35

Increased glucagon release in response to increased amino acids (metabolites). Proteins are digested in the gut and taken up into the blood as amino acids

Question 36

13. What is the effect of starvation, trauma, or vigorous exercise upon glucagon release and what is the hormone or metabolite directly affecting the a-cells?

Answer 36

Increased glucagon release in response to increased epinephrine and cortisol (hormones). The stress hormones tend to rise/fall together

Question 37

14. To the extent that it is known, explain the series of events following an increase in insulin that results in more glucose transporters in muscle and adipose tissue cell membranes.

Answer 37

• Insulin binds to the insulin binding site on the insulin receptor on the outer cell membrane. Binding to the alpha subunits of the receptor changes the conformation of beta-subunits inside the cell and activates the tyrosine kinase domains. Autophosphorylation of tyrosyl residues of the beta-subunit changes its conformation and provides a binding sites for the IRS (insulin receptor substrate)
• IRS proteins are then phosphorylated by the activated receptor at several tyrosyl residues creating several different binding sites for several proteins with different SH2 domains. The only we are interested in is phosphatidylinositol 3-kinase. The binding of the SH2 domain of the phosphatidylinositol 3-kinase to the tyrosyl phosphate site on the IRS activates the phosphatidylinositol 3-kinase
• Active phosphatidylinositol 3-kinase converts PI-4,5-bisP into PI-3,4,5-trisP on the inner surface of the cell membrane. PI-3,4,5-trisP serves to bind and activate the pathway containing protein kinase B. This pathway transfers GLUT-4 (glucose transporter 4) into the cell membrane and increases theuptake of glucose into adipose tissue cells and muscle cells.
• Other info: There are several different protein kinase Bs, and unfortunately, two of them are in our text. Their function is different. Also, the exact sequence of the effect of insulin upon GLUT-4 is not well worked out.
• A protein with a SH2 domain binds to both a phosphotyrosyl residue and ome of the amino acids around the phosphotyrosyl residue. That is, the SH2 and the protein with the phosphorylated residue must be complementary around the binding site. If there is a positive charge on one, there must be a negative charge on the other. Hydrophobic surfaces must be opposed to other hydrophobic areas. This is why a protein with an SH2 domains will not bind to most of the phosphotyrosyl residues in the cell

Question 38

15. To the extent that it is known, explain the effects of insulin upon cAMP cascade.

How would insulin affect the concentration of cAMP? Name the enzyme.

How would insulin affect the proteins phosphorylated as a result of the cAMP cascade? Name the type of enzymes.

Answer 38

• Insulin activates cAMP phosphodiesterase. This enzyme converts cAMP by 5’-AMP. Without cAMP, the cAMP cascade cannot activate protein kinase A (Fig 11.18)
• Insulin activates protein phosphatase, an enzyme that hydrolyzes seryl phosphates added by protein kinase (Fig 9.7). Dephosphorylation reverses the effect of the cAMP cascade
• To the extent that the cAMP cascade may be activated by glucagon, insulin inhibits the secretion of glucagon

Question 39

16. List all the intermediates in the signal transduction of glucagon from the binding of the ligand to the activation of a protein by phosphorylation.

Answer 39

• Glucagon binds to glucagon receptor on cell membrane and changes its conformation
• Change in conformation inside the cell allows binding of the glucagon receptor to heterotrimeric G protein, the exchange of GTP for GDP, and the dissociation of the alpha-subunit from the beta-gamma subunit (Fig 11.17)
• The Gs_a-subunit binds to the target enzyme, adenylyl cyclase, which produces cAMP
• cAMP, acting as an allosteric activator, binds to the regulatory subunits of protein kinase A and dissociates the regulatory subunits from the catalytic subunit of protein kinase A
• Protein kinase A phosphorylates the seryl residues of many enzymes, either activating or inhibiting their activity. Examples already covered are glycogen phosphorylase kinase, phosphofructokinase-2/fructose 2,6-bisphosphatase, pyruvate kinase, and acetyl CoA carboxylase

Question 40

17. One characteristic of a second messenger system is signal amplification! What does this statement mean?

Answer 40

To amplify is to increase the magnitude of the original signal. For a hormone and a second messenger system, the original hormone signal (concentration) would be increased in magnitude inside the cell with many steps in the cascade

For example: One glucagon can activate a number of G proteins. One G proein bound to adenylate cyclase can catalyze the formation of many cAMP molecules so that one glucagon molecule may be amplified to 10,000 cAMP molecules. Furthermore, one active protein kinase A molecule may result in the activation of 240 glycogen phosphorylase enzymes. In total, the single glucagon molecule activated 1,200,000 glycogen phosphorylase molecules

Question 41

18. When the glucagon concentration outside a liver cell is decreased suddenly, there is rapid change in the activation of many of the pathways influenced by glucagon. What is responsible for the rapid termination of signal?

Answer 41

• Glucagon is no longer stimulating receptors
• G protein hydrolyzes GTP to GDP and becomes inactive, no longer activating adenyl cyclase to make cAMP
• Increased insulin* activates phosphodiesterase, which wipes out the cAMP in the cell
• Increased insulin* activates protein phosphatase, and this dephosphorylates the proteins that were phosphorylated by protein kinase A
• *Usually when the glucagon concentration is low, the insulin concentration is high
• Glucagon is constantly begin destroyed by the liver

Question 42

19. What is the major second messenger systems associated with the a1-adrenergic receptor (Table 11.1: Gαq, activates phospholipase C)? How about the B1-, B2, and B3-adrenergic receptors?

Answer 42

• Binding of epinephrine to the α1-adrenergic receptors activates the Gαq subunit and phospholipase C in the membrane. This produces two second messengers: diacylglycerol and IP₃ systems (see Ch 11)
• Phosphoatidylinositol-4,5-bisphosphate → IP₃ + Diacylglycerol
• IP₃ leads to a release of Ca²⁺ from the endoplasmic reticulum. The increased Ca²⁺ activates the Ca²⁺-calmodulin and this in turns activates enzymes like glycogen phosphoylase kinase
• DAG also activates protein kinase and PKC phosphorylates target proteins
• Binding of epinephrine to B1-, B2, and B3-adrenergic receptors activates the Gα_s subunit, adenylate cyclase, cAMP, and protein kinase A

Question 43

20. Concerning Ann Sulin: She has type 2 diabetes and her blood insulin levels are within the normal range. Are her Β-cells secreting enough insulin? Are her muscle and adipose cells responding normally to insulin?

Answer 43

• Her beta cells are NOT secreting enough insulin. For a certain level of blood glucose, her insulin levels will always be lower than normal
• Her muscle, adipose cells, and all other cells are NOT responding normally to insulin because they are insulin-resistant. Insulin resistance is not primarily due to the number of insulin receptor but rather the lack of response from inside the cells. The response of the pathways is less than normal where something in the pathways of insulin-resistant cells stops them from responding as they normally should to insulin

Other info: Insulin levels are not valuable to a physician. Before diagnosis, insulin levels are probably high. After diagnosis, they may be high or normal. As the years go by, they will decrease to below normal. Do not confuse insulin resistance with insulin resistance syndrome. The latter is a set of syndromes like overweight, high BP, increased blood glucose, waist-hip ratio, body mass index, and insulin resistance. Insulin resistance syndrome and metabolic syndrome are synonymous

Question 44

21. Concerning Ann Sulin who has type 2 diabetes: explain one way in which high blood glucose changes the conformation of many types of proteins and may cause vascular disease.

Answer 44

Nonenzymatic glycosylation is the result of a sugar molecule bonding to a protein or lipid molecule without the controlling action of an enzyme. This causes retinopathy, nephropathy, neuropathy, and atherosclerosis leading to coronary artery disease – all symptoms common to diabetics with uncontrolled blood glucose levels. It has been shown that diabetics who consistently keep their A1C levels to below 8% are spared most of these symptoms

Question 45

22. Concerning Ann Sulin who has type 2 diabetes: Explain how taking a sulfonylurea drug will increase insulin output by the Β-cells.

Answer 45

• Sulfonurea drugs bind to and inhibit ATP-sensitive K⁺ channel on the membrane. This closes the channel and inhibits the flow of potassium ions from the cell
• Inhibited ATP=sensitive K⁺ channel leads to depolarization, which activates Ca²⁺ channels to open, causing an influx of Ca²⁺
• Increase in Ca²⁺ stimulates fusion of the insulin storage vesicles with the cell membrane and exocytosis of the insulin granules (precipitate), which results in more insulin released from the B-cells

Question 46

23. Concerning Ann Sulin who has type 2 diabetes: given a concentration of blood glucose, will she have a normal amount of insulin release? Will her blood insulin to glucose ratio be normal?

Answer 46

She will always have a lower-than-normal insulin release as well as blood insulin to glucose ratio. Type II diabetics produce less insulin and release it slower than normal

Question 47

24. Concerning Ann Sulin who has type 2 diabetes: What does insulin resistance mean?

Answer 47

Insulin resistance means that the metabolic pathways inside the cells are less responsive to insulin than in a normal person. Glucose uptake and utilization is below normal

Question 48

24. Concerning Ann Sulin who has type 2 diabetes: Is glucose uptake by liver, adipose and muscle cells normal?

Answer 48

Glucose uptake in muscle and adipose depends upon GLUT-4 in the membrane, and this is controlled by insulin. With insulin resistance, uptake is slower. Glucose uptake in muscle, adipose, and liver depends on the rate at which the cell can metabolize glucose and will be lower in a patient with Type II diabetes

Question 49

24. Concerning Ann Sulin who has type 2 diabetes: Is the release of fatty acids from adipose tissue normal?

Answer 49

The release of fatty acids from adipose cells is inhibited by glucose and activated by glucagon and other stress hormones. The inhibition by insulin will be less than normal, so more fatty acid will be mobilized. In addition, the concentration of glucagon will be greater due to the inhibition of alpha-cells by insulin decreasing. This results in a higher-than-normal concentration of blood glucagon that activates the release of fatty acids from adipose

Question 50

25. Concerning Ann Sulin who has type 2 diabetes: why does she have a higher than normal concentration of blood glucagon?

Answer 50

• She has high glucagon because not enough insulin is released and because of beta-cell insulin resistance
• The release of glucagon from alpha cells of the pancreas is controlled by levels of glucose and/or insulin in the bloodstream. Normally, an increase in either the glucose or insulin level in the blood inhibits glucagon secretion from the alpha-cells of the pancreas. As insulin levels decrease, so does the amount of inhibition on glucagon secretion. Type 2 diabetes produce less insulin overall and at a slower rate than they should at any given blood glucose level. Consequently, there is a diminished quantity of circulating insulin, which results in diminished inhibition of glucagon secretion
• Additionally, all the cells of Type 2 diabetics exhibit insulin resistance, in that they are less response than normal given any insulin level. The alpha cells are no exception, and they too exhibit a decreased response (decreased suppression of glucagon secretion) to the circulating insulin

Note: there is some question as to whether glucose directly inhibits glucagon release or whether it must act through insulin. Both occur, but to what degree? Dr. Y uses the indirect route (i.e., glucose raises insulin  insulin raises glucagon release). With Type 2 diabetes, increased glucose should lead to increased (but not increased enough) insulin. The “not high enough” insulin, together with insulin resistance, account for the high glucagon release. Even if blood glucose does have an important role in inhibiting glucagon release, it is not enough to inhibit increased glucagon release in Type 2 diabetes

Question 51

26. Concerning Bea Selmass: Explain why a patient with an insulinoma would have fasting hypoglycemia.

Answer 51

• An insulinoma is a tumor, usually benign and made up of specialized beta islets that constantly secrete insulin, causing hypoglycemia. The insulin secretion is not regulated by blood glucose, epinephrine, or anything else
• Usually, when a person enters the fasting state and blood glucose drops below 80 mg/dL, insulin secretion stops, and liver glycogenesis & gluconeogenesis begins in order to maintain the blood glucose levels. In a patient with insulinomnia, insulin never decreases, so glucagon secretion is continuously inhibited. Without glucagon, liver glycogenolysis and gluconeogenesis are not activated. Hypoglycemia ensues.
• The hypoglycemia is exacerbated by the uptake of glucose into muscle, adipose, and other tissues that are stimulated by insulin. Also since insulin inhibits fatty acid mobilization and utilization, fatty acids are not available for ATP synthesis. This greatly increases the use of glucose for ATP production, and the body quickly runs out of glucose

Other info: Patient develop symptoms such as headache, lethargy and blurred vision, especially when exercising or fasting. Severe hypoglycemia can cause seizures, comas, and neurological damage. When the glucose level drops to about 55mg/dL, this also triggers release of adrenaline by the adrenal glands with resultant adrenergic symptoms: palpitations, tachycardia, increased sweating, hunger, anxiety, and/or nausea

Question 52

27. Concerning Bea Selmass, who has an insulinoma: What effect would the hyperinsulinemia alone to have upon the release of glucagon from cells?

What effect did the combined effect of hyperinsulinemia and hypoglycemia have upon the release of glucagon from the alpha-cells?

Answer 52

• Insulin wins! Hyperinsulinemia alone would inhibit the release of glucagon from alpha-cells. Hypoglycemia would have two effects on the release of glucagon from alpha-cells:
  
  • Given the absence of insulin, and if the hypoglycemia occurs within 5 hours, it normally causes adrenaline secretion which should increase glucagon secretion
  • Stimulates glucagon release from the pancreas (also given the absence of insulin)
• • It is obvious that in the case of an insulinoma, the inhibition of insulin is stronger than the activation by low blood sugar and epinephrine