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Diabetes mellitus

Diabetes mellitus. Extremely large amount of water excretion Pissing evil High sugar content in the urine mellitus = “honey” Heterogeneous group of disease Insulin-dependent Noninsulin-dependent. Insulin-dependent diabetes. Type I diabetes Loss of beta cells Decreased insulin production

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Diabetes mellitus

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  1. Diabetes mellitus • Extremely large amount of water excretion • Pissing evil • High sugar content in the urine • mellitus = “honey” • Heterogeneous group of disease • Insulin-dependent • Noninsulin-dependent

  2. Insulin-dependent diabetes • Type I diabetes • Loss of beta cells • Decreased insulin production • Autoimmune disease against beta cells • Viral infection • 20 % of patients with diabetes mellitus • Requires insulin replacement

  3. Noninsulin-dependent diabetes • Type II diabetes • The majority of diabetes mellitus • More prevalent in some Native Americans • Lack of insulin response • Insulin resistance • Higher insulin concentrations • Decreased insulin receptor number (type A) • Immunity against insulin receptor (type B) • Postreceptor signaling defects

  4. Majority of adult-onset diabetes • Type II • Differences between type I and type II diabetes • Insulin secretion in response to secretagougues • Normal in type II • No insulin secretion in response to glucose in type II • Abnormal glucose recognition by the islet

  5. Insulin resistance • Immune response against insulin • Injection of animal insulin • Abnormal hormone • Decreased affinity to receptor • Abnormal proteolytic cleavage (familial hyperproinsulinemia) • Unprocessed protein (inability to remove C-peptide)

  6. Results of insulin resistance • Increased glycolysis • Lack of glycogen synthesis • Lack of substrate for hepatic ATP generation • Lack of glucose retention within the cell • Results in polyphagia • Polyuria and polydipsia • Increased lipolysis • Increased gluconeogenesis • Increased acetyl-CoA synthesis

  7. Increased acetyl-CoA synthesis • Increased condensation and generation of ketone bodies • Ketouria • ketosis • Increased urination • Loss of Na • Disturbance in bicarbonate buffering system • Could be fatal • Acidosis

  8. Relationship between diabetes and obesity • Upper body obesity • Hyperlipidemia • Hypertension • Diabetes • Adult-onset diabetes • More common in men • Fat distribution difference • Maybe androgen dependent

  9. Thyroid hormones

  10. Gross anatomy

  11. Biochemistry and synthesis of thyroid hormones • Formed as a complex between tyrosine and iodine • Iodine • Limited factor in terrestrial mammals • Stored in follicular cells against electrical gradient • Use of Na/I co-transporter and Na/K-ATPase pump • Oxidized by peroxidase • Incorporation in tyrosyl group of thyroglobulin (TG) • Formation of monoiodotyrosine and diiodotyrosine

  12. Formation of thyroxine • Oxidative coupling of iodinated tyrosines • Formation of T4 and small amount of T3 • Lysosomal digestion of TG • Fusion of colloid containing body with lysomomes • Formation of secondary lysosomes • Released via diffusion • Cytoplasm • Deiodinated • Extracellular space • Secretion

  13. Uptake and storage of thyroid hormones • Formation • Lumen of the follicle • Uptake • Pinocytosis • Storage • Initially in the colloid droplets

  14. Control of thyroid hormone secretion • Hypothalamus • TRH • Secreted in response to lowered ambient temperature • Increased metabolism to increase body temperature • TSH • Anterior pituitary gland • In response to TRH

  15. Secretion of TRH and TSH • Inhibited by T4 • Pro-TRH gene transcription • Loss of T4 • Increased Pro-TRH gene transcription • Increased release of TRH and related peptides

  16. Role of TSH • Binding of TSH to the receptors • Increased synthesis activity • Golgi apparatus and rough endoplasmic reticulum • Changes in the shape of cell (columnar) • Extremely critical • Increased cAMP production • Increased iodine incorporation into TG • Increased uptake • Increased pinocytosis

  17. Metabolism • In circulation • Water-insoluble hormones • Bound form (all proteins are synthesized by the liver) • Transthyretin (20 %) • TBG (70-75 %) • Albumin (5-10 %)

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