Deck 46: Insulin Function

Question 1

A 19-year-old man is brought to the emergency room unconscious and unresponsive. There are no visible signs of trauma or head injury. The attending physician orders blood work and administration of an IV bolus of glucose. The patient regains consciousness but remains unclear of how or why he passed out. History indicates the patient is not diabetic and does not take insulin shots. However, the physician suspects the patient passed out due to insulin-induced hypoglycemia. Analysis of the patient's blood for which of the following would best confirm the physician's suspicions?

A) C peptide
B) epinephrine
C) glucagon
D) glucose
E) ketones

Answer 1

C peptide

Question 2

You are testing the effects, on insulin function, to the addition of an unknown substance to adipocytes in culture. In the presence or absence of the compound you find that insulin binds to the adipocytes with equal affinity. Insulin alone results in a 5-fold increase in the rate of glucose uptake, above the basal rate. However, following addition of your test compound the rate of glucose uptake in response to insulin is only 0.5-fold above the basal rate. Your compound is actively taken up by the adipocytes and thus is likely exerting its effects intracellularly. Which of the following substances is your test compound most likely mimicking in this cell culture system?

A) ceramide
B) glucuronate
C) glucosamine
D) glucose
E) phosphatidic acid

Answer 2

ceramide

Question 3

Addition of which of the following compounds would be expected to result in the greatest increase in insulin resistance in adipocytes in culture under conditions of hyperglycemia and hyperinsulinemia?

A) fructose
B) galactose
C) glucosamine
D) glycine
E) sialic acid

Answer 3

glucosamine

Question 4

Type 1 diabetics frequently experience ketoacidosis. Administration of insulin decreases the serum concentration of ketone bodies in these patients via which of the following mechanisms?

A) decreasing formation of ketone bodies in skeletal muscle
B) decreasing lipolysis in adipose tissue
C) increasing hepatic activity of carnitine acyltransferase
D) increasing hepatic levels of acetyl-CoA
E) increasing hepatic oxidation of ketone bodies

Question 5

A 13-year-old adolescent boy with type 1 diabetes has a serum glucose concentration is 540 mg/dL. Several hours following IV administration of insulin, his serum glucose concentration decreases to 200 mg/dL. Which of the following mechanisms best explains the effect of the insulin signaling pathway on the GLUT4 transporter in this decrease resulting in the reduced serum glucose?

A) it activates GLUT4 by a cAMP-dependent mechanism
B) it increases GLUT4 mRNA
C) it increase the K
M of GLUT4 for glucose
D) it induces a conformational change in GLUT4
E) it promotes GLUT4 mobilization to the plasma membrane

Question 6

Pancreatic oxidation of glucose results in increased release of insulin. This mechanism is referred to as glucose-stimulated insulin secretion (GSIS). A defect in which of the following proteins would be expected to exert the greatest negative effect on GSIS?

A) AMPK
B) ABCC8
C) glucokinase
D) GLUT2
E) KCNJ11

Question 7

Recent evidence has identified an enzyme involved in the modification of GLUT2 in pancreatic b-cells that is critically important for glucose-stimulated insulin secretion (GSIS). Which of the following represents this modification necessary for GLUT2 action?

A) acetylation
B) acylation
C) glycosylation
D) methylation
E) phosphorylation

Question 8

Insulin action results in the increased expression of several genes as well as the decreased expression of others. One consequence of these global gene expression changes is increased fatty acid synthesis due, in part, to the inhibition of expression of which of the following genes?

A) CYP7A1 (cholesterol 7α-hydroxylase)
B) glucokinase
C) liver pyruvate kinase (LPK)
D) PEPCK
E) PDK4 (pyruvate dehydrogenase kinase 4)

Question 9

Insulin, being a growth factor, increases the rate of protein synthesis, in part, by increasing the activity of the kinase mTOR. Activation of mTOR in response to insulin receptor stimulation requires inhibition of which of the following upstream signaling molecules?

A) AMPK
B) GSK3
C) PKB/Akt
D) PI3K
E) TSC1/TSC2

Question 10

Which of the following represents a major target tissue for the action of insulin reflecting its ability to regulate circulating levels of blood glucose?

A) brain
B) heart
C) kidney
D) skeletal muscle
E) testis

Question 11

Activation of insulin receptors by binding of insulin results in numerous changes in the activity of other signaling proteins. Some of these changes are increases in activity, some are decreases. Of the following enzymes, which one has an increased level of activity after insulin binds its receptor?

A) GSK3
B) glycogen synthase
C) glycogen phosphorylase
D) PKA
E) protein phosphatase inhibitor 1 (PPI-1)

Question 12

The incretins are hormones that are released in response to the consumption of food. Which of the following represents one of the major effects of incretin release from intestinal epithelial cells?

A) activation of gastric emptying ensuring release of ingested food
B) enhancement in adipocyte triacylglycerol synthesis
C) enhancement of insulin secretion from the pancreas
D) repression of pancreatic cell proliferation
E) stimulation of gastric acid secretion to aid in digestion

Question 13

Insulin receptor activation results in an increase in the flux of glucose into glycogen in skeletal muscle. A defect in which of the following proteins involved in glycogen homeostasis would be expected to result in the greatest deficit in insulinmediated glycogenesis in these cells?

A) glucose 6-phosphatase
B) glycogen synthase-phosphorylase kinase
C) glycogen phosphorylase
D) protein phosphatase inhibitor 1 (PPI-1)
E) protein targeting glycogen (PTG)

Question 14

Although the major metabolic effect of insulin is to promote fuel storage following meals, this hormone also has growth factor activity. One of the growth-promoting responses to insulin action is an increase in the rate of translation. Which of the following proteins of translation is a target of insulin-mediated action, the consequence of which is a reduced level of phosphorylation and thus increased activity?

A) 4EBP
B) eEF-2
C) eIF-2
D) eIF-2B
E) eRF

Question 15

Based on your understanding of the role of insulin in the body, expression of which of the following enzymes would be expected to be reduced as a consequence of the actions of insulin?

A) acetyl-CoA carboxylase
B) hepatic glucokinase
C) lipoprotein lipase
D) PEP carboxykinase
E) pyruvate kinase

Question 16

Which of the following activities, relating to glucose homeostasis, is directly attributable to the actions of glucagon-like peptide-1 (GLP-1)?

A) decreased fatty acid release from adipose tissue
B) decreased glucagon release from the pancreas
C) increased transit of carbohydrates through the intestines
D) stimulated degradation of hepatic glycogen stores
E) unmasking of GLUT4 transporters in skeletal muscle

Question 17

You are studying adipocytes isolated via biopsy from a 12-year-old male patient who exhibits chronic hyperglycemia but with normal circulating levels of insulin. Your studies of these cells demonstrate that the density of insulin receptors is similar to adipocytes from control volunteers, binding kinetics are also identical, and the receptors become autophosphorylated in response to insulin binding. Given these observations it is most likely that there is a defect in which of the following insulin signal transduction proteins leading to the observed hyperglycemia in the subject?

A) glycogen synthase kinase 3, GSK3
B) mammalian target of rapamycin, mTOR
C) phosphodiesterase, PDE
D) PIP₃-dependent protein kinase, PDK1
E) protein kinase B (PKB/Akt)

Question 18

In a comparison study of 2 related cell lines you find that one responds normally to insulin while the other has an impaired response. You discover that both cell lines bind insulin with equal affinity but that the impaired response is manifest in an inability to recruit the insulin receptor substrate 1 (IRS1) protein to the receptor. This would most likely be due to which of the following?

A) decreased activation of the tyrosine phosphatase activity of the receptor preventing removal of phosphate from the IRS1 docking site
B) inability of the receptor to phosphorylate the G-protein, RAS
C) loss of activation of PLCb in response to insulin-binding receptor
D) serine phosphorylation of the insulin receptor preventing IRS1 from binding
E) tyrosine phosphorylation of the insulin receptor leading to the loss of the IRS1 binding site

Question 19

Exogenous peripherally injected insulin differs from endogenously secreted insulin in a number of aspects, including which of the following?

A) achieves a higher concentration in the periphery than in the liver, contrary to endogenous insulin
B) contains C peptide, which is missing from secreted endogenous insulin
C) is able to bypass insulin resistance observed with endogenous insulin
D) is always extracted from animal sources and therefore is less effective due to sequence differences and anti-insulin antibodies
E) is in the form of proinsulin, whereas endogenous insulin has had C peptide removed

Question 20

A 14-year-old adolescent girl with a 2-year history of type 1 diabetes is brought to the ER 1 hour after awakening from sleep at 2:30 am in a cold sweat, tremulous and confused. She normally selfadministers 4 injections of insulin daily, and the last injection was administered before she went to bed. Measurement of her blood glucose concentration indicates it is 40 mg/dL. Following an injection of glucagon, her serum glucose concentration increases to 175 mg/dL, and she shows clinical improvement. The beneficial effect of glucagon in this patient results from which of the following actions of this hormone in the liver?

A) adenylate cyclase stimulation
B) guanylate cyclase stimulation
C) intranuclear binding of hormone receptor to DNA
D) serine/threonine kinase activation
E) tyrosine kinase activation

Question 21

Which of the following metabolic processes is promoted by insulin?

A) catabolism of muscle protein
B) fatty acid oxidation
C) gluconeogenesis
D) glycogenesis
E) lipolysis

Question 22

You are examining the responses of adipocytes in culture to the addition of various peptide hormones. You find that after the addition of one hormone in your study there is an increase in glucose uptake from the media. Which of the following is the most likely initial event triggered by the addition of the test hormone, leading to the observed effects?

A) activation of adenylate cyclase by the receptor
B) autophosphorylation of threonine residues in the receptor
C) interaction of the receptor with a signal cascade protein
D) interaction of the receptor with the glucose transporter
E) translocation of the hormone receptor complex to the nucleus

Question 23

Insulin is synthesized in theb-cells of the pancreas as a proinsulin molecule. In order for this proinsulin to be biologically active, which of the following posttranslational modifications of the hormone is required?

A) acetylation of the α-amino group
B) binding of zinc ions
C) cleavage of peptide bonds
D) oxidation of sulfhydryl groups
E) phosphorylation of tyrosine residues

Question 24

You are carrying out experiments to examine insulin-stimulated glucose uptake in isolated skeletal muscle cells. You know that insulin first binds to its receptor on the plasma membrane of these cells triggering an increase in phosphatidylinositol-3 kinase (PI3K) activity. The net effect of increased PI3K activity is insertion of subcellular membranes containing GLUT4 protein into the plasma membrane. Which of the following is the most likely first intracellular step in this signaling cascade?

A) activation of PI3K
B) activation of phospholipase Cb (PLCb)
C) autophosphorylation of the receptor tyrosine kinase
D) phosphorylation of insulin receptor substrate 1 (IRS1)
E) phosphorylation of mitogen-activated protein kinase (MAPK)

Question 25

You are studying the responses of myocytes in culture to the addition of insulin. Normally in myocytes when insulin binds, several proteins are phosphorylated by kinases. You discover that several target proteins are not appropriately modified in your cells. Which of the following is most likely not occurring in your cell culture in response to insulin thereby, explaining the lack of target protein phosphorylation?

A) action of a G-protein in the plasma membrane
B) release of Ca²⁺ from the endoplasmic reticulum
C) release of diacylglycerol from phosphatidylinositol
D) translocation of the glucose transporter to the plasma membrane
E) tyrosine kinase activity of the insulin receptor