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 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 %)