METABOLIC CHANGES IN WELL FEED STATE, STARVATION ,DM

METABOLIC CHANGES IN WELL FEED STATE

All body cells use glucose for energy. To maintain this constant source of energy, blood

glucose levels must be kept between 3.3-6.1 mmol/L

Several hormones, help to maintain this level between 3.3-6.1mmol/L, include insulin, glucagon

The insulin and the glucagon together maintain a constant level of glucose in the blood

INSULIN

Insulin is a small peptide hormone produced by beta cells of the pancreas

Molecular weight of 5808 Da 51 amino acids ,two amino acid chains A and B chains are linked together by two disulfide

bonds A chain consists of 21 amino acids and the B chain

of 30 amino acids.

ACTION OF INSULIN ON CARBOHYDRATE,

Facilitates the transport of glucose into muscle and adipose cells.

Facilitates the conversion of glucose to glycogen for storage in the liver and muscle by ↑ glycogen synthase.

Decreases the breakdown and release of glucose from glycogen by the liver by↓ glycogen phospharylase activity.

ACTION OF INSULIN ON PROTEIN.

Stimulates protein synthesis Inhibits protein breakdown; diminishes

gluconeogenesis by ↓ pyruvate carboxylases activity ↓PEP carboxkinases. ↓ Fructose 1,6 bisphosphates. ↓glucose 6 phosphates.

ACTION OF INSULIN ON FAT METABOLISM

Inhibition of FFA mobilization from adipose tissue via suppression of lipolysis by inhibiting activity of hormone sensitive lipase

Inhibition of plasma FFA uptake and oxidation via suppression of lipolysis

Inhibition of hepatic VLDL synthesisSuppression of circulating ketone body concentrations

Activation of adipose lipoprotein lipaseStimulation of lipogenesis

INSULIN SECRETION

GLUCAGON

Alpha cells of the islets of Langerhans ,pancreases.

Blood glucose concentration falls.Mol wt of 3485 Da.Large polypeptide ,29 amino acids.Most important of these functions is to increase

the blood glucose concentration ,an effect that is exactly the opposite that of insulin

The major effects on glucose metabolism breakdown of liver glycogen (glycogenolysis) ↑glycogen

phosphorylases activity. increase gluconeogenesis in the liver by

↑ pyruvate carboxylases ↑ PEP carboxkinases ↑ Fructose 1,6 bisphosphates ↑ Fructose 1,6 bisphosphates

Also involved in stimulating hormone sensitive lipase and

promoting lipolysis.

Glucagon binds to the glucagon receptor,( a G protein-coupled receptor).• conformational change

• replacement of the GDP molecule that was bound to the α subunit with a GTP molecule.

• releasing of the α subunit from the β and γ subunits.

• The alpha subunit specifically activates the next enzyme in the cascade, adenylate cyclase.

• cyclic adenosine monophosphate (cAMP), which activates protein kinase A (cAMP-dependent protein kinase).

• This enzyme, in turn, activates phosphorylase kinase, which, in turn, phosphorylates glycogen phosphorylase, converting into the active form called phosphorylase A

• .Phosphorylase A is the enzyme responsible for the release of glucose-1-phosphate from glycogen polymers.

METABOLIC CHANGES IN STARVATION Early ,Intermediate, Advance stages of starvation

Early stage (2 days)• Glycogenolysis and gluconeogenesis are imp source of blood glucose.• Energy from alternate source (β oxdn FA, KB).

Intermediate stage (24 days)• glycogen stores mostly depleted not serve as source blood glucose.• FA ,KB supplied to heart, kidney ,muscles.

Advanced stage (>24 days)• KB supplies to heart, kidney ,muscles is decreased , limited to brain only.• Heart, kidney ,muscles on FA as main source.• Gluconeogenesis will enhanced due to increased activity of enzymes

pyruvate carboxylase, fructose 1,6 bisphosphates,

Fig 19.1019-44

Figure 16.18

DIABETES MELLITUS (DM)

SUMMARY

INSULIN GLUCAGON

Glucose uptake stimulates Inhibition

Glycogenesis stimulates Inhibition

Glycogenolysis stimulates stimulates

Gluconeogenesis inhibition stimulates

Protein synthesis stimulates inhibition

Protein degradation Inhibition stimulates

Lipolysis Inhibition Stimulates

Ketone body Inhibition Stimulates

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