Insulin – Metabolic Actions

INSULIN – METABOLIC ACTIONS

Q. 1 Which of the following statements about insulin is NOT correct? Insulin acts to

 A Increase the rate of synthesis of liver glucokinase
 B Enhance the rate of transport of amino acids into muscle
 C Increase activity of intracellular tyrosine Kinase
 D Increase the rate of transport of glucose into brain cells
Q. 1 Which of the following statements about insulin is NOT correct? Insulin acts to

 A Increase the rate of synthesis of liver glucokinase
 B Enhance the rate of transport of amino acids into muscle
 C Increase activity of intracellular tyrosine Kinase
 D Increase the rate of transport of glucose into brain cells
Ans. D

Explanation:

Insulin increases the rate of glucokinase synthesis, which promotes the uptake of glucose in the liver by increasing the concentration gradient. This process helps to lower blood glucose levels after a carbohydrate meal and sets the stage for the synthesis of glycogen and fatty acids by the liver. Insulin also promotes the transport of amino acids and glucose into muscle cells by recruiting an increased number of specific transporter proteins into the membrane. This process also helps to lower blood glucose and promotes anabolic activity in the muscle cell. Conversely, when blood glucose levels and insulin levels are low, muscle is less able to take up glucose, thus conserving it for the brain and red blood cells. These tissues are normally dependent on glucose as an energy source; this dependence is complete for the red blood cell, whereas the brain can utilize ketones for fuel in the starvation state. The binding of insulin to its receptor activates tyrosine kinase activity on an intracellular domain of the receptor. This auto phosphorylates the receptor as well as other proteins. Induction of a phosphorylation on tyrosine is also characteristic of growth factors. The protein kinases activated by cyclic adenosine monophosphate (cAMP; protein kinase A) or by calcium and diacylglycerol (protein kinase C) differ in that they phosphorylate seryl or threonyl residues; however, in all cases the phosphorylations represent the manner by which the cell responds to the signal carried by the hormones. Another manifestation of the anabolic activity of insulin is increased transport of potassium along with glucose into cells. This may lead to a serious depletion of serum potassium, potentially resulting in death. Insulin plus glucose is one of the modalities of therapy for hyperkalemia.


Q. 2

Which of the following physiological action is NOT done by insulin?

 A

Glycogen synthesis

 B

Glycolysis

 C

Lipogenesis

 D

Ketogenesis

Q. 2

Which of the following physiological action is NOT done by insulin?

 A

Glycogen synthesis

 B

Glycolysis

 C

Lipogenesis

 D

Ketogenesis

Ans. D

Explanation:

Ketogenesis occurs in insulin deficiency.
 
Principal Actions of Insulin:
 
Rapid (seconds)
  • Increased transport of glucose, amino acids, and K+ into insulin-sensitive cells
Intermediate (minutes)
  • Stimulation of protein synthesis
  • Inhibition of protein degradation
  • Activation of glycolytic enzymes and glycogen synthase
  • Inhibition of phosphorylase and gluconeogenic enzymes
Delayed (hours)
  • Increase in mRNAs for lipogenic and other enzymes
Ref: Barrett K.E., Barman S.M., Boitano S., Brooks H.L. (2012). Chapter 24. Endocrine Functions of the Pancreas & Regulation of Carbohydrate Metabolism. In K.E. Barrett, S.M. Barman, S. Boitano, H.L. Brooks (Eds), Ganong’s Review of Medical Physiology, 24e.

Q. 3

Insulin acts on which enzyme in glycoysis-

 A

Glucokinase

 B

Hexokinase

 C

Glucose 6-Phosphatase

 D

Adenylate kinase

Q. 3

Insulin acts on which enzyme in glycoysis-

 A

Glucokinase

 B

Hexokinase

 C

Glucose 6-Phosphatase

 D

Adenylate kinase

Ans. A

Explanation:

A i.e. Glucokinase

In glycolysis insulin acts on hexokinase IV (i.e. glucokinase) and hexokinase IIQ but not on other (I & III) hexokinase


Q. 4

Rapid infusion of insulin causes

 A

Hyper kalemia

 B

Hypokalemia

 C

Hypernatremia

 D

Hyponatremia

Q. 4

Rapid infusion of insulin causes

 A

Hyper kalemia

 B

Hypokalemia

 C

Hypernatremia

 D

Hyponatremia

Ans. B

Explanation:

B i.e. Hypokalemia

Insulin promotes the transport of K+ (potassium) and phosphate (PO4) into cells leading to hypokalemia and hypophosphatemiaQ, (i.e. L K+ &           .

Effect of Insulin on K+ and PO43-

– Insulin increases the transport of potassium (K+) from plasma into cells by stimulating the Na+-K+ – ATPase pumps in cell membranes of muscle, liver and adipocytes. This results in lowering of plasma (extracellular) K+ concentration i.e. hypokalemiaQ.

Infusions of insulin (and glucose) significantly lower the plasma K+ levels in normal individuals and are used for temporaty relief of hyperkalemia in patients with renal failure, waiting for dialysis.

– Hypokalemia often develops when patients with diabetic acidosis are treated with insulin.

– Insulin induces rapid entery of glucose into cells, a process which is followed by phosphorylation reaction in glycolytic pathway, lowering the intracellular concentration of inorganic phosphate, and therefore promotes phosphate (P034) entry into cells. This is how insulin 1/t hypophosphatemia (decrease plasma /ECF PO43-)


Q. 5

True about Insulin action is:

 A

Causes neoglucogenesis

 B

Not useful for growth & development

 C

Required for transport of glucose, aminoacid, K+ & Na+0

 D

Catabolic hormone

Q. 5

True about Insulin action is:

 A

Causes neoglucogenesis

 B

Not useful for growth & development

 C

Required for transport of glucose, aminoacid, K+ & Na+0

 D

Catabolic hormone

Ans. C

Explanation:

C i.e. Required for transport of glucose, aminoacid, K+ & Na+


Q. 6

Insulin promotes lipogenesis by all of the following ways except:

 A

Decreasing intracellular cAMP

 B

Increasing the transport of glucose into the cell

 C

Inhibits pyruvate dehydrogenase

 D

Increases activity of acetyl-CoA carboxylase

Q. 6

Insulin promotes lipogenesis by all of the following ways except:

 A

Decreasing intracellular cAMP

 B

Increasing the transport of glucose into the cell

 C

Inhibits pyruvate dehydrogenase

 D

Increases activity of acetyl-CoA carboxylase

Ans. C

Explanation:

C i.e. Inhibits Pyruvate dehydrogenase


Q. 7

All are actions of insulin except :

 A

Gluconeogenesis

 B

Glycolysis

 C

Glycogenesis

 D

Lipogenesis

Q. 7

All are actions of insulin except :

 A

Gluconeogenesis

 B

Glycolysis

 C

Glycogenesis

 D

Lipogenesis

Ans. A

Explanation:

A i.e. Gluconeogenesis


Q. 8

Not done by insulin:

 A

Glycogen synthesis

 B

Glycolysis

 C

Lipogenesis

 D

Ketogenesis

Q. 8

Not done by insulin:

 A

Glycogen synthesis

 B

Glycolysis

 C

Lipogenesis

 D

Ketogenesis

Ans. D

Explanation:

D i.e. Ketogenesis


Q. 9

What is role of insulin in lipid metabolism:

 A

Active lipoprotein lipase

 B

Increase lipolysis

 C

Activate hormone sensitive lipase

 D

All

Q. 9

What is role of insulin in lipid metabolism:

 A

Active lipoprotein lipase

 B

Increase lipolysis

 C

Activate hormone sensitive lipase

 D

All

Ans. A

Explanation:

A  i.e. Active lipoprotein lipase


Q. 10

Insulin increases the activities of all of the following enzymes, EXCEPT:

 A

Glucokinase

 B

Pyruvate carboxylase

 C

Glycogen synthase

 D

Acetyl-CoA carboxylase

Q. 10

Insulin increases the activities of all of the following enzymes, EXCEPT:

 A

Glucokinase

 B

Pyruvate carboxylase

 C

Glycogen synthase

 D

Acetyl-CoA carboxylase

Ans. B

Explanation:

B i.e. Pyruvate carboxylase

Insulin increases lipogenesis (i.e. FA, TG & glycerol P synthesis) and decrease lipolysis and so free fatty acid levelQ

–  Insulin activate acetyl CoA carboxylase (rate limiting enzyme of FA synthesis), activate lipoprotein lipase (so increasing TG synthesis) but inhibits hormone sensitive lipase.Q

– Insulin decreases gluconeogenesis by inactivating pyruvate carboxylaseQ etc and increases glycolysis by inducing phosphofructokinase and pyruvate kinase enzymesQ.


Q. 11

Insulin mediated glucose uptake occurs through

 A

GLUT-1

 B

GLUT -2

 C

GLUT- 3

 D

GLUT -4

Q. 11

Insulin mediated glucose uptake occurs through

 A

GLUT-1

 B

GLUT -2

 C

GLUT- 3

 D

GLUT -4

Ans. D

Explanation:

D i.e. GLUT-4


Q. 12

Insulin does not facilitate glucose uptake in the following except :

 A

Liver

 B

Heart

 C

RBC

 D

Kidney

Q. 12

Insulin does not facilitate glucose uptake in the following except :

 A

Liver

 B

Heart

 C

RBC

 D

Kidney

Ans. B

Explanation:

B i.e. Heart


Q. 13

Insulin acts on glucose metabolism by:

 A

T permeability of glucose across cell membrane

 B

permeability across cell membrane against glucose gradient

 C

T permeability of renal cells

 D

T glucose transport to brain

Q. 13

Insulin acts on glucose metabolism by:

 A

T permeability of glucose across cell membrane

 B

permeability across cell membrane against glucose gradient

 C

T permeability of renal cells

 D

T glucose transport to brain

Ans. B

Explanation:

B i.e. T permeability across cell membrane against glucose gradient

Insulin increases glucose uptake by increasing the number of glucose transporter in cell membrane. Direct insulin stimulated glucose uptake is mediated by Glut 4 and is seen only in:

  1. Muscle: Skeletal muscleQ and cardiac muscleQ
  2. Adipose tissueQ

Glucose Transporters In Mammals

Facilitated

Bidirection

Diffusion

Function

Major Sites of

Expression

Km

GLUT 1

Basal glucose uptake

–  Placenta, blood –

brain barrier, Red

cells, kidneys

1-2

GLUT 2

B cell glucose sensor;

transport out of

intestinal & renal

epithelial cells.

–  B cells of islets,

Liver, Small

intestine, Kidney

12-20

GLUT 3

Basal glucose uptake

–  Brain, placenta,

kidney

<1

GLUT 4

Insulin stimulated

glucose uptakeQ

– Skeletal & cardiac

muscleQ

– Adipose tissueQ

5

GLUT 5

Fructose transport

– Jejunum, Sperm

1-2

GLUT 6

None

– Pseudogene

‑

GLUT 7

Glucose 6-PO4

transporter in

endoplasmic

reticulum

–   Liver

‑

Secondary Active Transport Na+ glucose cotransport

(unidirectional -transporter)

SGLT-1

Active uptake of

glucose against

Small intestine, renal

tubule

0.1 – 1.0

SGLT-2

concentration

gradient

Renal tubule

1.6


Q. 14

In glycolysis, insulin affects all of the following en­zymes except:       

 A

Phosphofructokinase

 B

Pyruvate kinase

 C

Glucokinase

 D

Hexokinase

Q. 14

In glycolysis, insulin affects all of the following en­zymes except:       

 A

Phosphofructokinase

 B

Pyruvate kinase

 C

Glucokinase

 D

Hexokinase

Ans. D

Explanation:

 

The activation as well as the quantities of certain key enzymes of glycolysis, namely glucokinase (NOT hexokinase), phosphofructokinase and pyruvate kinase are increased by insulin.


Q. 15

Insulin is required for glucose transport in all of the following except: 

March 2009

 A

RBC

 B

Skeletal muscles

 C

Adipose tissue

 D

Heart muscles

Q. 15

Insulin is required for glucose transport in all of the following except: 

March 2009

 A

RBC

 B

Skeletal muscles

 C

Adipose tissue

 D

Heart muscles

Ans. A

Explanation:

Ans. A: RBC

Insulin facilitates entry of glucose into muscle, adipose, and several other tissues.

The only mechanism by which cells can take up glucose is by facilitated diffusion through a family of hexose transporters. In many tissues – muscle being a prime example – the major transporter used for uptake of glucose (called GLUT4) is made available in the plasma membrane through the action of insulin.


Q. 16

Regulation of lipid metabolism by insulin lacks which of the following feature:  

 A

Reduced activity of HMG CoA synthetase

 B

Increased release of fatty acids from stored fat in adipose tissue

 C

Increased availability of glycerol-3-phosphate

 D

Increased Acetyl CoA carboxylase activity

Q. 16

Regulation of lipid metabolism by insulin lacks which of the following feature:  

 A

Reduced activity of HMG CoA synthetase

 B

Increased release of fatty acids from stored fat in adipose tissue

 C

Increased availability of glycerol-3-phosphate

 D

Increased Acetyl CoA carboxylase activity

Ans. B

Explanation:

 

The net effect of insulin on lipid metabolism is to reduce the release of fatty acids from the stored fat.

Among the tissues, adipose tissue is the most sensitive to the action of the insulin

Lipogenesis

  • It is the process by which acetyl-CoA is converted to fats.
  • The former is an intermediate stage in metabolism of simple sugars, such as glucose.
  • Through lipogenesis, the energy can be efficiently stored in the form of fats.
  • Lipogenesis encompasses the processes of fatty acid synthesis and subsequent triglyceride synthesis (when fatty acids are esterified with glycerol to form fats).
  • The products are secreted from the liver in the form of very-low-density lipoproteins (VLDL)
  • Fatty acids synthesis starts with acetyl-CoA and builds up by the addition of two carbon units.
  • The synthesis occurs in the cytoplasm in contrast to the degradation (oxidation), which occurs in the mitochondria.
  • Many of the enzymes for the fatty acid synthesis are organized into a multienzyme complex called fatty acid synthetase.

Control and regulation

  • Insulin is an indicator of the blood sugar level of the body, as its concentration increases proportionally with blood sugar levels.
  • Thus, a large insulin level is associated with the fed state.
  • As one might expect, therefore, it increases the rate of storage pathways, such as lipogenesis.
  • Insulin stimulates lipogenesis in two main ways:
  • The enzymes pyruvate dehydrogenase (PDH), which forms acetyl-CoA, and acetyl-CoA carboxylase (ACC), which forms malonyl-CoA, are obvious control points.
  • These are activated by insulin.
  • So a high insulin level leads to an overall increase in the levels of malonyl-CoA, which is the substrate required for fatty acids synthesis.
  • PDH dephosphorylation

Q. 17

Which enzyme’s activity is increased in low insulin/glucagon level?

 A

Hexokinase

 B

Glucokinase

 C

Glucose-6-phosphatase

 D

Pyruvate kinase

Q. 17

Which enzyme’s activity is increased in low insulin/glucagon level?

 A

Hexokinase

 B

Glucokinase

 C

Glucose-6-phosphatase

 D

Pyruvate kinase

Ans. C

Explanation:

 

Insulin suppresses glucose-6-phosphatase gene.

Glucose-6-phosphatase activity is increased in low insulin/glucagon level.

Glucocorticoids, glucagon, epinephrine are inducers of glucose-6-phosphatase whereas insulin is repressor.

Insulin upregulates the transcription of glucokinase, phosphofructokinase, and pyruvate kinase, while glucagon downregulates their transcription.

Glucose-6-phosphatase plays an important role in the regulation of hepatic glucose production, and insulin suppresses glucose-6-phosphatase gene.


Q. 18

Insulin mediated glucose transport is seen in ‑

 A

Adipose tissue

 B

Brain

 C

RBC

 D

Kidney

Q. 18

Insulin mediated glucose transport is seen in ‑

 A

Adipose tissue

 B

Brain

 C

RBC

 D

Kidney

Ans. A

Explanation:

Ans. is ‘a’ i.e., Adipose tissue

  • Insulin stimulates the uptake of glucose by myocytes (skeletal muscle, cardiac muscles), adipocytes (adipose tissue) and hepatocytes. Tissues that do not depend on insulin for glucose uptake include brain, erythrocytes (RBC), the epithelial cells of kidney & intestine, Liver, and Cornea & lens of eye.
  • The mechanism through which insulin increases glucose uptake is different in different tissues. In the muscle and adipose tissues, insulin increase facilitated diffusion by increasing glucose transporter (GLUT4) on the cell membrane.
  • In the liver, insulin stimulates glucose entry into hepatocytes indirectly by induction of glucokinase so that the glucose entering the liver cells is promptly converted to glucose – 6 – phosphate (glucose trapping). This keeps the intracellular glucose concentration low and favours entry of glucose into the liver. Thus, though the liver do not depend on insulin for glucose uptake, insulin stimulates glucose entry into hepatocytes. That means glucose entery can occur in liver without the action of insulin, but this is facilitated by insulin. On the other hand, myocytes (skeletal and cardiac muslces) and adipocytes (adipose tissue) are dependent on insulin for glucose uptake.

Q. 19

Insulin dependent glucose uptake is not seen in ‑

 A

Skeletal muscles

 B

Heart

 C

Adipose tissue

 D

Kidney

Q. 19

Insulin dependent glucose uptake is not seen in ‑

 A

Skeletal muscles

 B

Heart

 C

Adipose tissue

 D

Kidney

Ans. D

Explanation:

 

Insulin dependent glucose uptake is through GLUT-4 and is seen in :‑

1) Skeletal muscles

2) Cardiac muscles (heart)

3) Adipose tissue


Q. 20

Insulin causes ‑

 A

Inhibition of glycolysis

 B

Gluconeogenesis

 C

Induction of lipogenesis

 D

Increased glycogenolysis

Q. 20

Insulin causes ‑

 A

Inhibition of glycolysis

 B

Gluconeogenesis

 C

Induction of lipogenesis

 D

Increased glycogenolysis

Ans. C

Explanation:

Ans. is ‘c’ i.e., Induction of lipogenesis

ACTIONS OF INSULIN

  • Insulin affects the metabolism of carbohydrates, lipids and proteins.

Effects on carbohydrate metabolism

The overall effect of insulin is to decrease blood glucose level. Insulin increases the utilization of glucose and decreases its production by its following actions : –

i) Stimulation of oxidation of glucose by glycolysis especially in the liver and skeletal muscle.

ii) Stimulation of glycogenesis i.e., insulin favours conversion of glucose into its storage form, glycogen. This action is seen in both liver and muscles.

iii) Inhibition of gluconeogenesis.

  • Insulin stimulates the uptake of glucose by myocytes (skeletal muscle, cardiac muscles), adipocytes (adipose tissue) and hepatocytes. Tissues that do not depend on insulin for glucose uptake include brain, erythrocytes (RBC), the epithelial cells of kidney & intestine, Liver, and Cornea & lens of eye.
  • The mechanism through which insulin increases glucose uptake is different in different tissues. In the muscle and adipose tissues, insulin increase facilitated diffusion by increasing glucose transporter (GLUT4 ) on the cell membrane.
  • In the liver, insulin stimulates glucose entry into hepatocytes indirectly by induction of glucokinase so that the glucose entering the liver cells is promptly converted to glucose – 6 – phosphate (glucose trapping). This keeps the intracellular glucose concentration low and favours entry of glucose into the liver. Thus, though the liver do not depend on insulin for glucose uptake, insulin stimulates glucose entry into hepatocytes. That means glucose entery can occur in liver without the action of insulin, but this is facilitated by insulin. On the other hand, myocytes (skeletal and cardiac muslces) and adipocytes (adipose tissue) are dependent on insulin for glucose uptake.

Increased uptake of glucose in the glucose has following effects :-

i) T Glycolysis :- It is due to induction of key enzymes of glycolysis by insulin. These key enzymes are glucokinase, phosphofructokinase and pyruvate kinase.

ii) Increased glycogen synthesis (glycogenesis) :- It is due to induction of glycogen synthase.

iii) Decreased glycogen break-down (Glycogenolysis) : – It is due to inhibition of enzyme phosphorylase.

iv) Decreased gluconeogenesis :- It is due to inhibition of enzymes Pyruvate carboxylase, PEP carboxykinase, fructose 1, 6-bisphosphatase, glucose – 6 – phosphates.

Effects on lipid metabolism

  • Insulin induces lipogenesis by inducing enzyme acetyl CoA carboxylase, the rate limiting enzyme in fatty acid synthesis. Triglyceride synthesis is increased by induction of lipoprotein lipase.
  • Lipolysis (13-oxidation) is decreased due to inhibition of hormone sensitive lipase, so that the fat in the adipose tissue is not broken down. Thus free fatty acid and glycerol are decreased. Because of antilipolytic action insulin decreases ketogenesis.

There are two important lipases : –

i)  Lipoprotein lipase : – It hydrolysis the triglycerides of chylomicrons and VLDL into free fatty acid and glycerol in the vessels of skeletal muscles, cardiac muscles and adipose tissue. There FFA is taken up by the cells of these tissue and is converted back into the triglyceride and the FFA is stored as triglyceride. So, lipoprotein lipase is involved in the synthesis of triglyceride. Lipoprotein lipase is stimulated by insulin, therefore insulin stimulates triglyceride synthesis.

ii) Hormone sensitive lipase : – It is involved in lipolysis and cause degradation of stored triglyceride of adipose tissue into FFA and glycerol. FFA comes out into the blood raising the FFA levels of blood. Insulin inhibits hormone sensitive lipase therefore decreases FFA levels of blood.

Effects on protein metabolism

  • Insulin stimulates synthesis of protein (anabolism) and inhibits protein breakdown (catabolism). Insulin increases the active transport of many amino acids into the tissue. In addition insulin increases protein synthesis by increasing the rate of synthesis of mRNA.

Q. 21

Enzyme inhibited by insulin ‑

 A

Glucokinase

 B

PFK-1

 C

Glycogen phosphorylase

 D

Glycogen synthase

Q. 21

Enzyme inhibited by insulin ‑

 A

Glucokinase

 B

PFK-1

 C

Glycogen phosphorylase

 D

Glycogen synthase

Ans. C

Explanation:

Q. 22

Insulin dependent entry of glucose is seen in ‑

 A

Liver

 B

Brain

 C

Heart

 D

Kidney

Q. 22

Insulin dependent entry of glucose is seen in ‑

 A

Liver

 B

Brain

 C

Heart

 D

Kidney

Ans. C

Explanation:

Ans. is ‘c’ i.e., Heart 



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