Diabetes mellitus Extremely large amount of water excretion –Pissing evil High sugar content in the urine –mellitus = “honey” Heterogeneous group of disease.

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• Autoimmune disease against beta cells• Viral infection

– 20 % of patients with diabetes mellitus– Requires insulin replacement

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

• 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

• 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)

• 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

• 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

Relationship between diabetes and obesity

• Upper body obesity– Hyperlipidemia– Hypertension– Diabetes

• Adult-onset diabetes– More common in men

• Fat distribution difference– Maybe androgen dependent

Thyroid hormones

Gross anatomy

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

• 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

• Uptake and storage of thyroid hormones– Formation

• Lumen of the follicle

– Uptake• Pinocytosis

– Storage• Initially in the colloid droplets

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

• 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

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

Metabolism

• In circulation– Water-insoluble hormones

• Bound form (all proteins are synthesized by the liver)

– Transthyretin (20 %)– TBG (70-75 %)– Albumin (5-10 %)