Glucose Homeostasis TBL (1)

GLUCOSE

HOMEOSTASIS

TBL

. Human homeostasis is an internal equilibrium or balance system that monitors and regulates the complex functions of the body, ensuring that a normal state is maintained.

Normal blood glucose level is 60 - 110mg/dl.

Maintenance of normal level is a function of different tissues as well as so many hormones.

ADIPOSE TISSUE

MUSCLE

BLOOD

GLUCOSE (diet)

BRAIN

CO2

GLC

FATTY ACIDS (diet)

PANCREAS

Insulin GLC

TG

FA

Pyruvate

Glucose

insulin

- insulin[3]

CO2

GLC

insulin

LIVER

KETONE BODIES

Figure 4. The glucose\fatty acid cycle – well fed state

+

++

• Role of tissues in glucose homeostasis :

• Role of GIT.

• Role of liver.

• Role of kidneys.

• Role of Adipose tissue.

• Role of skletal muscles.

Hormonal regulation of blood glucose

( Glucose homeostasis)

Insulin(Hypoglcemic)

Antiinsulin( Hyperglycemic)

-Glucagon-Epinephrine

-Glucocorticoids-Growth hormone

-Thyroid hormones

A- Insulin: *It is secreted by the -cells of pancreatic islets in

response to hyperglycemia. *It produces its effects through the following

mechanisms:- - It increases the uptake of glucose in muscles

and adipose tissue. - It increases utilization of glucose (oxidation,

glycogenesis and lipogenesis) in different tissues.

- It decreases output of glucose by liver (decreases glycogenolysis and gluconeogenesis).

B- Anti-Insulin hormones (counter regulatory hormones):

1. Glucagon:

* It is produced by a-cells of pancreatic islets.

* Its secretion is increased by fasting or any drop in blood glucose.

Acts through formation of cAMP, leading to

increased glycogenolysis and gluconeogenesis.

inhibition of glycolysis and glycogenesis.

Insulin/ glucagon ratio is the main regulator of blood glucose.

2. Epinephrine: ( hyperglycemic)

Produced by adrenal medulla and secreted in large amounts in cases of stress, trauma, severe exercise, hypoxia, anesthesia (emergency hormone).

- It increases glycogenolysis (through cAMP) in liver and muscles and inhibits glycogenesis.

- It increases F.A. release and oxidation.

- It decreases the uptake of glucose by the tissues.

Increased secretion of adrenaline can produce D.M. (emotional or stress D.M.)

3. Cortisol: Secreted by the adrenal cortex.

- It stimulates protein catabolism, and gluconeogenesis from amino acids.

- In extrahepatic tissues, it decreases glucose utilization.

4. Growth hormone (GH): - Secreted by the anterior pituitary gland in response to

abnormal low blood glucose level.

- Hyper secretion of GH can produce DM (pituitary DM)

THYROID HORMONE: THYROXINE INCREASES ALL ASPECTS OF METABOLISM.

(+) insulin secretion. (+)insulin catabolism

(+) GLC absorption by intestine.

(+) GLC uptake & utilization.

(+) glycogenolysis

(+) gluconeogenesis.

Thyroxine

Excess thyroxine causes hyperglycemia.

Insulin Glucagon Epi-nephrine

Cortisol G.H.

Stimulus for release

•Hyper-glycemia.

•Hypo-glycemia.

•Hypo-glycemia.

•Stress.

•Exercise.

•Hypo-glycemia.

I-GLC consumptioni-GLC entry •(+) in adipose

T., muscle.liver

# uptake

uptake

uptake

(in mus.)

ii-GLC utilization:

•Glycolysis

•PDH

•HMS

•Induces & activates (glucokinase, PFK1, PK )

•Activates PDH

•Induces G6PDH

•Represses & inactivates (PFK1, PK ).

# utilization by extra-hepatic tissues.

utilization


Cortisol G.H.

iii-storage:

glycogenesis

•Induces &

•Activates

Glycogen synthase.

•Inactivates glycogen synthase.

•Inactivates glycogen synthase.

# #

II-GLC productioni-Glycogenolysis

(-)

•Inactivates glycogen phosphorylase (dephosphorylation)

(+)

•Activates liver glycogen phosphorylase (not mus.)

(+)

•Activates liver & muscle glycogen phosphorylase.

(+)

(+)

ii-Gluconeo-genesis

•Represses

4 key enz (PC, PEPCK, F1,6 diphosphatase, G-6 -phosphatase)

•Induces

4 key

enzymes

•Induces

4 key

enzymes

•induces 4 key

enzymes

•Induces4 key enzymes


Cortisol G.H.

Lipid metabolism:I- lipogenesis (+) # #

# #

II-lipolysis (-)•no glycerol

•no excess FA

(+) (+) (+)

(+)

Protein metabolism:

I-synthesis(+)

# # # #

II-catabolism (-) # # (+)•Releases a.a.

•Activates trans-aminases.

(+)•Induces liver trans-aminases


Cortisol G.H.

I-GLC consumption:GLC entry & GLC utilization & storage:

(+) (-) (-) (-) (-)

II-GLC output:

Glycogenolysis & gluconeogenesis.

(-)

(+)

(+) (+) (+)

Net effect Hypo-glycemic hormone

Hyper-glycemic Hormone




Diabetes mellitus if:

Gastrointestinal tract regulates glucose level in blood by :

a)Allows gradual absorbance and utilization of glucose.

b)Allows sudden rise in glucose level in blood.

c) The rate of glucose absorption is 10 mg/kg weight.

d)Decrease insulin secretion.

Oral glucose stimulates insulin secretion more than I.V one because:

a) I.V glucose inhibits β pancreatic cells.

b) Oral glucose stimulates intestinal glucagon that stimulates β pancreatic cells.

c) Oral glucose increases the blood glucose rapidly that stimulates insulin secretion.

d)I.V glucose inhibit s intestinal hormones that stimulate insulin secretion.

Regarding the role of the liver in glucose homeostasis , all the following are true Except :

a)Liver is one of the most user of glucose in postabsorptive state.

b) In fasting , the liver is the main producer of glucose.

c) In postabsorptive state glycogenolysis is an active process.

d)Glycolysis is an active process in postabsorptive state .

The Kidney has an important role in glucose homeostasis :

a) It prevents the loss of glucose in urine whatever its blood level.

b)It shares in supplying blood glucose during fasting state.

c) It is the main user of glucose.

d)It is responsible for excretion of glucose in physiological range.

All the following about epinephrine are true Except :

a) It stimulates liver and muscle glycogenolysis.

b)It stimulates lipolysis.

c) It increases glucose uptake by the tissues.

d)It can produce emotional glucosuria.

Which hormone lowers blood sugar levels by increasing the rate of entry of glucose into the cells?

a. Growth hormone

b. Glucagon

c. adrenalin

d. insulin

A person was admitted to the hospital with abnormally high blood sugar and an abnormally high sugar content in his urine. Which hormone is deficient in this person?

a. Epinephrin

b. Parathyroid hormone

c. Glucagon

d. Insulin

Insulin increases the uptake of glucose in:

a. Muscles and liver

b. Muscles and Kidney

c. Muscles and adipose tissue

d. Liver and adipose tissue.

If a person consumes excess calories in the form of carbohydrates, what is the fate of the excess carbohydrates?

a. If glycogen stores are full, the carbohydrates are converted into amino acids.

b. If glycogen stores are full, the carbohydrates are converted to fatty acids and stored as triacylglycerols.

c. The carbohydrates are excreted without being metabolized.

d. The carbohydrates are converted to ketone bodies to be utilized by the brain.

# Glucagon plays a homeostatic role in the body by

A. facilitating glucose uptake into skeletal muscle.

B. causing the activation of liver phosphorylase.

C. activating adenylate cyclase in skeletal muscle cells.

D. causing the activation of liver pyruvate dehydrogenase.

E. stimulating muscle glycogenolysis during intense exercise.

Name the following :a) The main hormone stimulates gluconeogenesis.

b) Blood sugar level above which glucose is excreted in urine.

c) Glucosuria inspite of normal blood glucose level.

d) A test used to detect the ability of the body to utilise glucose.

Write false or true in front of the following statements:

a) Insulin is needed for glucose entry in liver.

b) In carbohydrate deficiency, lipolysis is stimulated.

c) Excess glucose is stored in adipose tissue as triglyceride.

d)During fasting, , muscles oxidizes fatty acids for energy production.

e)Muscles is an important organ for gluconeogenesis.

f) Muscles produce lactate and amino acids for gluconeogenesis.

g) Insulin indirectly stimulates glucose uptake by the liver.

h)Glucagon is a hyperglycemic hormone.

-Free glucose released from muscle contributes significantly to the alleviation of hypoglycemia

- Hepatic glycogenolysis is a primary source of blood glucose during a period of

48 h fasting.

GLYCOSURIADefinition

Types:

1. Glucosuria

A- hyperglycemic glucosuria:

- D.M.

- epinephrine glucosuria.

- alimentary glucosuria.

- experimental glucosuria.

GLYCOSURIA

B- Normoglycemic glucosuria:

- congenital renal glucosuria.

- aquired renal disease.

- experimental glucosuria (Phlorhizin).

2. Fructosuria:

- alimentary fructosuria.

- essential fructosuria.

GLYCOSURIA

3. Galactosuria:

- alimentary galactosuria.

- galactosemia.

4. Lactosuria.

Time in minutes

Glucose concentration

Glucose Homeostasis TBL (1)

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