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Prevalence of Diabetes in Race & Ethnic Groups. Increase in diabetes in 1990’s. The Prevalence of Diabetes in Native American Populations. Insulin comes from the Pancreas. Elongated tissue nestled within intestines and between kidneys/adrenals. -Cells Produce and Secrete Insulin
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Insulin comes from the Pancreas Elongated tissue nestled within intestines and between kidneys/adrenals • -Cells Produce and Secrete Insulin • Primary target tissue cites include: • hepatic cells (liver) • muscle cells • adipocytes (fat) • Insulin primarily released in response to a rise in blood glucose levels
Insulin Insulin Receptor Glucose
Insulin Glucose Insulin Receptor IRS-1 IRS-2 IRS-3 IRS-4 PI3K PIP3 AKT-1 AKT-2 AKT-3
Hyperinsulinemia Protein tyrosine phosphatases (PTPs) Serine Phosphorylation Ligand-induced downregulation Tyrosine Phosphorylation IRS-1 IRS-2 IRS-3 IRS-4 Glucose
Hyperinsulinemia→ decreases expressionof IRS-1 and IRS-2 Protein tyrosine phosphatases (PTPs) → dephophorylates important tyrosine residues → reducing activity Serine Phosphorylation → interaction with IRS Proteins → downregulates IR function →modifies kinase activity of IRS protein Ligand-induced downregulation→ internalization and degradation IR IRS-1 IRS-2 IRS-3 IRS-4 Glucose
Phosphatase PTEN SHIP2 IRS-1 IRS-2 IRS-3 IRS-4 Glucose PI3K PIP3
Phosphatase→ dephosphrylates PIP3 PTEN → dephosphrylates PIP3 SHIP2→ dephosphrylates PIP3 IRS-1 IRS-2 IRS-3 IRS-4 Glucose PI3K PIP3
IRS-1 IRS-2 IRS-3 IRS-4 Glucose PI3K PIP3 GLUT4 AKT-1 Glucose Uptake AKT-2 ↑Glucose Synthesis AKT-3 Cell Differentiation ↓Gluconeogenesis ↑Protein Synthesis
IRS-1 IRS-2 IRS-3 IRS-4 Glucose PI3K PIP3 GLUT4 AKT-1 Glucose Uptake AKT-2 ↑Glucose Synthesis AKT-3 Cell Differentiation ↓Gluconeogenesis ↑Protein Synthesis
IRS-1 IRS-2 IRS-3 IRS-4 PI3K PIP3 AKT-1 Glucose Uptake AKT-2 Glucose Synthesis AKT-3 Cell Differentiation Gluconeogenesis Protein Synthesis
TNFα IL-6 FFA IRS-1 IRS-3 IRS-2 IRS-4 PI3K PIP3 AKT-1 Glucose Uptake AKT-2 Glucose Synthesis AKT-3 Cell Differentiation Gluconeogenesis Protein Synthesis
CARBOHYDRATE METABOLISM Liver & Muscle Glycogenolysis Hyperglycemia Glucoseurea-Osmotic Diuresis Fluid & Electrolyte Loss Dehydration
CARBOHYDRATE METABOLISM Hemoconcentration Peripheral Circulatory Failure Hypotension Renal Blood Flow Renal Failure Coma Death
LIPID METABOLISM Lipogenesis Lypolysis Lipemia Ketogenesis Ketonemia MetablicAcidosis Ketonuria Hyperpena Dehydration
LIPID METABOLISM Hemoconcentration Peripheral Circulatory Failure Hypotension Renal Blood Flow Renal Failure Coma Death
PROTEIN METABOLISM Protein Catabolism Aminoacidemia Gluconeogenesis Urinary Nitrogen Loss of cellular K+ Net loss of K+
Prevalence of Diabetic Retinopathy after Diagnosis of Diabetes Fong, D.S., et al. Diabetes Care 27:S84, 2004
AUTONOMIC NEUROPATHY • heart and blood vessels • digestive system • urinary tract • sex organs • sweat glands • eyes
AUTONOMIC NEUROPATHY • Unawareness of Hypoglycemia • Postural Hypotension • Unresponsive Heart Rate • Maldistribution of Blood Flow • Alternating Constipation and Uncontrolled diarrhea • Gastroparesis (stomach to empty too slowly) • persistent nausea and vomiting, bloating, and loss of appetite. • fluctuations in blood glucose levels • Swallowing difficulties • Incomplete bladder emptying • bacteria to grow in the bladder and kidneys and causing urinary tract infections. • Urinary incontinence • Decrease sexual response in men and women • Lack of or perfuse sweating • pupils less responsive to changes in light
PERIPHERAL NEUROPATHY • toes • feet • legs • hands • arms
PERIPHERAL NEUROPATHY • numbness or insensitivity to pain or temperature • a tingling, burning, or prickling sensation • sharp pains or cramps • extreme sensitivity to touch, even a light touch • loss of balance and coordination
FOCAL NEUROPATHY • eyes • facial muscles • ears • pelvis and lower back • thighs • abdomen
FOCAL NEUROPATHY • inability to focus the eye • double vision • aching behind one eye • paralysis on one side of the face (Bell's palsy) • severe pain in the lower back or pelvis • pain in the front of a thigh • pain in the chest, stomach, or flank • pain on the outside of the shin or inside the foot • chest or abdominal pain that is sometimes mistaken for heart disease, heart attack, or appendicitis
PROXIMAL NEUROPATHY • thighs • hips • buttocks
PROXIMAL NEUROPATHY • pain in either the thighs, hips, buttocks, or legs, usually on one side of the body • weakness in the legs, manifested by an inability to go from a sitting to a standing position without help
EXERCISE PREVENTION Incidence Rates of type 2 (/ 10,000 man-years Helmich, S.P. et al. New England J Medicine 325:147-152, 199
Regular Walking Decreases Morbidity Rates by 50% in Diabetics Gregg, E.W., Arch Intern Med 163:1440-1447, 2003