Download 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
• 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
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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 %)