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Glucocorticoids on Gluconeogenesis

Glucocorticoids on Gluconeogenesis. Glucocorticoids. Hormones produced by the adrenal glands Acts on carbohydrate, lipid, and protein metabolism 21-carbon steroid Promote gluconeogenesis Predominant glucocorticoid- cortisol. Glucocorticoid. Adrenal glands.

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Glucocorticoids on Gluconeogenesis

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  1. Glucocorticoids on Gluconeogenesis

  2. Glucocorticoids • Hormones produced by the adrenal glands • Acts on carbohydrate, lipid, and protein metabolism • 21-carbon steroid • Promote gluconeogenesis • Predominant glucocorticoid- cortisol

  3. Glucocorticoid

  4. Adrenal glands • Located medial to the upper poles of kidneys

  5. 3 Layers of Adrenal Cortex • Zona glomerulosa • Zona fasciculata-cortisol is made • Zona reticularis

  6. Main artery supply • Inferior phrenic artery • Renal arteries • Aorta artery

  7. How is cortisol made • Most powerful glucocorticoid in man • Synthesized from cholesterol • Converted to delta 5 pregeneolone • Converted to progesterone • After 3 hydroxylations, cortisol is formed

  8. Glucocorticoid secretion • Through negative feedback loop • Hypothalamus secretes corticotrophin-releasing hormone (CRH) • Pituitary is stimulated for adrenocorticotropin (ACTH) • Pituitary ACTH stimulates the release of glucocorticoid

  9. Synthetic compounds • Cortisone • Hydroxcortisone • Prednisone • Prednisolone • Methlyprednisolone • Dexamethasone • Betamethasone • Used for tx of Addison’s disease

  10. Glucocorticoid Receptor Binding • Affect target cells by interacting receptor proteins • Enter cell through simple diffusion • Glucocorticoids bind to intracellular glucocorticoid receptors

  11. 1st Mechanism • Glucocorticoid regulatory element is binding to specific sites in nuclear DNA • Called glucocorticoid response elements. • Located near target genes

  12. Glucocorticoid Transcription Factors 2nd mechansim • Results in transcription factors of mRNA • Transcription of near by genes are affected by binding of glucocorticoid receptors to hormone response elements or proteins • Stimulates or inhibits transcription • Once inside cell the steroid is bound to glucocorticoid receptor • Single chain polypeptide • Hormone-receptor binds with DNA once the steriod is bound

  13. Glucocorticoids on Glucose Metabolsim • Glucocorticoids present in all tissues • Involved in glucose metabolsim and increase & maintain normal glucose levels in blood by other processes • Gluconeogenesis in the liver • Stimulation of fat breakdown in adipose tissue • Inhibition of glucose • Fat storage in cells

  14. Glucocorticoids on Carbohydrate Metabolism • They inhibit peripheral glucose uptake in muscle and adipose tissue • They affect decrease protein synthesis and increase protein breakdown in tissues • Muscle • Fat • Lymphoid • Resulting in increase release of amino acids

  15. Glucocorticoid Hormones on Gluconeogenic Enzymes • Act directly on synthesis of gluconeogneic enzymes • Supply of peripheral tissues and target cells are increased by glucocorticoid hormones • Gluconeogneic enymes and control protein are induced by glucocorticoid hormones • Overnight fast • Release of amino acids from sketal muscles is stimulated by decrease of insulin and increase of glucocorticoid levels in blood • Stimulate amino acid uptake in the liver

  16. Glucocorticoids Stimulation Gluconeogenesis • Gluconeogenesis and glycogen synthesis in liver is stimulated • Signals PEPCK, F-1,6-biPase,G-6-Pase, and glycogen synthase • Entry of pyruvate in liver mitochondria • Stimulate gluconeogenesis by Mobilizationof amino acids in peripheral tissues

  17. Glucocorticoids reaction on Phosphoenolpyruvate (PEP) • Increase PEPCK in the liver • PEPCK controls how glucocorticoids regulate hepatic gluconeogenesis • Glucocorticoids increase • release of substrates for gluconeogenesis from peripheral tissues, mainly muscle • Hepatic responsiveness to the hormone glucagon • Peripheral amino acid uptake and protein synthesis is enhanced

  18. Glucocorticoids on Glucose-6-phosphatase (G-6-Pase) • Activate G-6-Pase • Activate fructose-1,6-diphosphatase in the liver

  19. Glucocorticoids on Hepatic Storage • Hepatic storage of glucose by glycogen • Indicator of glucocorticoid action is accumulation of glycogen in the liver • Glycogen synthase is activated • Conversion of blood glucose into liver glycogen is increased by cortisol

  20. Glucocorticoids on Glycogen Metabolsim • 2 key enzymes glycogen synthetase & glycogen phosphorylase controls glycogen metabolism in the liver • Exist in 2 forms, one active, other inactive • Glycogen-mobilizing enzyme glycogen phosphorylase is inactivated by glucocorticoids

  21. Glucocortiocoids on Glycogen Metabolism • Glycogen synthetase is stimulated by glucocorticoids • Promoting conversion from inactive b form to active a form

  22. Glucocorticoids • Glucocorticoids have effect on gluconeogenesis • A lot of unknown factors of how gluconeogenesis is effected • The body cannot survive without glucocorticoids or gluconeogenesis • Unbalance of either can create diseases in man and animals

  23. Glucocorticoids • Studies regarding effects of glucocorticoids on gluconeogenesis allows • Physicians and Veterinarians to be able to treat certain adrenal diseases • Cortisol is present in every body tissue • Some diseases are fatal • Cushing’s and Addison’s disease

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