SM_184b: Intermediary Metabolism

Question 1

Insulin is a ___ hormone with a short half life released from ___

Answer 1

Insulin is a peptide hormone with a short half life released from beta cells in the Islets of Langerhans

Question 2

Insulin receptors are ____

Answer 2

Insulin receptors are tyrosine kinases

Question 3

Describe process that occurs after insulin binds to insulin receptors

Answer 3

Process that occurs after insulin binds to insulin receptors

1. Insulin binds to insulin receptors (RTKs)
2. Glucose uptake in target tissues by transposition of membrane glucose transporter GLUT-4
3. Stimulation of glycogen synthesis and inhibition of glycogenolysis in the liver
4. Induction of genes regulating storage of energy carriers in the form of glycogen and triglyceride synthesis, mainly in muscle and liver
5. Induction of genes responsible for increased protein synthesis (anabolic)

Question 4

Insulin dependent tissues are ____, ____, and ____

Answer 4

Insulin dependent tissues are muscle, fat, and liver

Question 5

Insulin is continually synthesized by ____

Answer 5

Insulin is continually synthesized by beta cells in the Islets of Langerhans

(secreted from beta cells)

Question 6

____ is produced in equimolar concentration from insulin’s precursor proinsulin and released along with insulin

Answer 6

C-peptide is produced in equimolar concentration from insulin’s precursor proinsulin and released along with insulin

Question 7

____ are a better marker for endogenous insulin production than insulin given the longer half life of c-peptide

Answer 7

Serum C-peptide levels are a better marker for endogenous insulin production than insulin given the longer half life of c-peptide

Question 8

____ is the main regulator of the rate of insulin release from secretory vesicles

Answer 8

Plasma glucose level is the main regulator of the rate of insulin release from secretory vesicles

Question 9

Describe the mechanism for regulation of insulin release via plasma glucose

Answer 9

Mechanism for regulation of insulin release via plasma glucose

1. Plasma glucose is sensed by beta cells via free entry of glucose in beta cells (GLUT 2 transporter)
2. Oxidative metabolism of glucose via glycolysis and entering the Krebs cycle (citric acid cycle) leading to production of ATP
3. Resulting increase in ATP / ADP ratio is sensed by ATP sensitive potassium channels on the cell membrane of beta cells (K_ATP channels)
4. K_ATP channels are inhibited and increase their rate of closure in response to a rising ATP / ADP ratio -> higher rate of depolarization
5. Cell depolarization activates VG-gated Ca channels -> rise in cellular [Ca] via Ca entry into the cell membrane, augmented by Ca release from ER (triggered by the initial Ca influx)
6. Rise in intracellular [Ca] triggers fusion of insulin and c-peptide containing vesicles with the cell membrane exocytosis of prestored insulin and c-peptide
7. Additional factors facilitate or inhibit insulin release and production from beta cells

Question 10

___ facilitates insulin release from beta cells

Answer 10

GLP-1 facilitates insulin release from beta cells

Question 11

Glucagon is secreted by ____ in the ____

Answer 11

Glucagon is secreted by alpha cells in the Islets of Langerhans

Question 12

Describe action of glucagon

Answer 12

Glucagon

• Counteracts insulin with respect to glucose uptake and metabolism
• Stimulates insulin secretion from beta cells -> prevents excessive hyperglycemia in response to glucagon

Question 13

Ghrelin is released mainly by cells in the ____ and ____

Answer 13

Ghrelin is released mainly by cells in the stomach and intestinal wall

Question 14

Ghrelin levels rise during ____, inducing ____ and promoting ____

Answer 14

Ghrelin levels rise during fasting, inducing hunger and promoting energy conservation

Question 15

____ is secreted by adipose tissue proportional to its mass

Answer 15

Leptin is secreted by adipose tissue proportional to its mass

Question 16

___ induces satiety

Answer 16

Leptin induces satiety

(sensitivity to leptin’s effect may be decreased in persons with chronic obesity)

Question 17

Inactivating mutations in the genes encoding either ____ or the ____ lead to massive obesity

Answer 17

Inactivating mutations in the genes encoding either leptin or the leptin receptor lead to massive obesity

(currently being explored for treatment of obesity and / or diabetes)

Question 18

_____ is secreted by cells in the intestine in response to food intake and facilitates insulin secretion from beta cells following oral intake

Answer 18

Glucagon like peptide 1 (GLP-1) is secreted by cells in the intestine in response to food intake and facilitates insulin secretion from beta cells following oral intake

Question 19

GLP-1 agonists are used for the treatment of ____

Answer 19

GLP-1 agonists are used for the treatment of diabetes mellitus

Question 20

Fed state involves higher ____ levels and lower ____ levels

Answer 20

Fed state involves higher insulin levels and lower glugoxe levels

Question 21

In the ___ state, glucose uptake, protein, glycogen, and triglyceride synthesis is stimulated in insulin sensitive target tissue (liver, muscle, adipocytes)

Answer 21

In the fed state, glucose uptake, protein, glycogen, and triglyceride synthesis is stimulated in insulin sensitive target tissue (liver, muscle, adipocytes)

Question 22

In the fed state, lower levels of orexigenic hormones such as ____ and higher levels of ____ promote satiety

Answer 22

In the fed state, lower levels of orexigenic hormones such as ghrelin and higher levels of leptin promote satiety

Question 23

In the fasting state, ____ levels are maintained in the normal range by decreasing plasma insulin levels, while there are higher ___ levels

Answer 23

In the fasting state, glucose levels are maintained in the normal range by decreasing plasma insulin levels, while there are higher glucagon levels

Question 24

In the fasting state, ___ is released from the liver

Answer 24

In the fasting state, glucose is released from the liver

(glycogenolysis, gluconeogenesis)

Question 25

In the fasting state, ____ are mobilized from adipose tissue and either oxidized in peripheral tissue or converted to ketones in the liver

Answer 25

In the fasting state, liver are mobilized from adipose tissue and either oxidized in peripheral tissue or converted to ketones in the liver

Question 26

In the fasting state, ____ are mobilized from body protein stores and serve as substrate for liver ____

Answer 26

In the fasting state, amino acids are mobilized from body protein stores and serve as substrate for liver gluconeogenesis

Question 27

In the fasting state, higher levels of orexigenic hormones such as ____ and decreasing levels of ____ promote hunger

Answer 27

In the fasting state, higher levels of orexigenic hormones such as ghrelin and decreasing levels of leptin promote hunger

Question 28

____ and ____ are increased in the fasting state

Answer 28

Glucagon and ghrelin are increased in the fasting state

Question 29

____ and ____ are increased in the fed state

Answer 29

Insulin and leptin are increased in the fed state

Question 30

Describe principle hormones of the Islets of Langerhans

Answer 30

Islets of Langerhans

• Glucagon: alpha cells
• Insulin: beta cells
• Somatostatin: d cells
• Pancreatic polypeptide: F cells

Question 31

____, ____, and ____ stimulate glucose secretion while ____ and ____ inhibit insulin secretion

Answer 31

Glucose, GLP-1, and glucagon stimulate glucose secretion while inflammatory cytokines and norepinephrine inhibit insulin secretion

Question 32

Describe the importants about insulin

Answer 32

Insulin

Question 33

____ and ____ inhibit glucagon secretion

Answer 33

Glucose and insulin inhibit glucagon secretion

Question 34

GLP-1 and GIP are ____, act through ____, and are degraded by ____

Answer 34

GLP-1 and GIP are peptide hormones secreted by the L-cells in the jejunum in response to feeding, act through GPCR, and are degraded by several peptidases including DPP-4

Question 35

Describe effects of GLP-1 and GIP

Answer 35

GLP-1 and GIP

• Enhance glucose stimulated insulin secretion
• Inhibit glucagon secretion
• Delay gastric emptying
• Induce satiety

Question 36

Leptin is a peptide hormone mainly secreted by ____ and acts through ____

Answer 36

Leptin is a peptide hormone mainly secreted by adipocytes and acts through cytokine activated cell membrane receptor class (JAK / STAT mediated)

Question 37

Ghrelin is a peptide hormone secreted by ____ and ____

Answer 37

Ghrelin is a peptide hormone secreted by epsilon cells (Islets of Langerhans) and gastric cells

Question 38

Ghrelin has effects of ____ and ____

Answer 38

Ghrelin has effects of inducing hunger and decreasing energy expenditure

Question 39

___ has greatest energy density

Answer 39

Fat (9 kcal/g) has greatest energy density

Carbohydrates and proteins: 4 kcal/g

Question 40

Insulin increases with ___

Answer 40

Insulin increases with meals

(returns to higher baseline level of insulin resistance)