Insulin and glucagon work together to maintain blood glucose levels between 3.3-6.1 mmol/L. Insulin is produced by the pancreas and facilitates glucose uptake and storage, while inhibiting gluconeogenesis. Glucagon is also produced by the pancreas and has opposing effects, stimulating gluconeogenesis and glycogenolysis to increase blood glucose. In starvation, glycogen stores are depleted after 2 days and fatty acids and ketone bodies provide energy, with gluconeogenesis enhanced after 24 days to supply glucose to vital organs.

1. METABOLIC CHANGES IN WELL FEED
STATE, STARVATION ,DM

2. 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

3. 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.

4. 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.

5. 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.

6. 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 synthesis
Suppression of circulating ketone body concentrations
 Activation of adipose lipoprotein lipase
Stimulation of lipogenesis

7. INSULIN SECRETION

9. 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

10.  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.

12.  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.

13. 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,

14. Fig 19.10
19-44

15. DIABETES MELLITUS (DM)
Figure 16.18

17. SUMMARY

18. 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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