1. Exams & Grading: 85% of the final grade: Exam scores from each of the three Sections will represent one-third of a total of 85% of the final grade for the course. Two exams will be administered in Section I, while one exam each will be given in Sections II & III. Sectional exams will be based on Tuesday-Friday lectures and employ a mix of short answer & essay questions. 10% of the final grade: The Final Exam on the “Integrative Perspective on Diabetes” will comprise 10% of the final grade. 5% of the final grade: The average score for the written responses to pre-assigned topics for Monday Discussions will comprise a total of 5% of the final grade. A traditional numerical scoring system will be used to generate a final letter grade - A= 90- 100% B=80-89% C=70--79%, D=60-69%, and F= 59% or less. FIS 2006

2. diabetes Type I –Autoimmune destruction of β-cells of pancreas Type II –Insulin resistance coupled with deficient release hyperglycemia & hyperlipidemia leading to atherosclerosis, neuropathy & infection

3. FIS 2006 (Diabetes) Version date: Aug 03, 2006 Final Exam: Integrative Perspective on Diabetes - 1 0% Final Grade Types of Questions: Contrast the etiologies of Type I & Type II diabetes, and discuss the mechanisms for the metabolic derangements leading to hyperglycemia and hyperlipidemia. Focus on a specific organ system (vascular, neural, host-defense) subjected to long-standing hyperglycemia, hyperlipidemia and other abnormalities secondary to poorly controlled Type I or II diabetes: - Discuss the mechanisms for pathology; - Discuss the mechanisms for pharmacological prophylaxis and/or treatment of organ system dysfunction.

4. FIS Organization: Exam #1- Basic Principles → diabetes Exam #2- Neurobiology → diabetes Exam #3- Endocrinology→ diabetes Exam #4- Immunology & Bacterial Pathogenesis → diabetes ↓ (Exam #5: final)

5. FIS 2006 (Diabetes) Lectures: Sept 2 - Diabetes & Polyphagia Oct 06 - Insulin Oct 10 - Counter Regulatory Hormones Oct 18, 18 & 20 - Homeostasis & Responses to External Environment Nov 17 – Immunology of Diabetes Monday Discussions: (student-driven lecture questions, student-driven journal clubs & faculty-driven discussion of relevance of lectures to diabetes). Resource Text: Ellenberg & Rifkin’s DIABETES MELLITUS, sixth edition, Porte et al., Neurobiology Sept 11 - Diabetes & Neuropathy Journal Club Organization Sept 18 - Diabetes & Neuropathy Journal Club Sept 25 - Diabetes & Neuropathy Journal Club Oct 02 - Diabetes, Erectile Dysfunction & Viagra Basic Principles & Endocrinology Aug 28- Diabetes & Atherosclerosis Oct 09 - Diabetes, Insulin Resistance & Metabolic Syndrome Oct 16 – Pharmacological Management of Diabetes Oct 23 - Diabetes, Insulin Resistance & Polycystic Ovary Syndrome Immunology & Bacterial Pathogenesis: Nov 27 - Immunology of Diabetes Dec 04- Infections & Diabetes

6. FIS & Diabetes: Type I Diabetes: Autoimmune destruction of β-cells of pancreas Type II Diabetes: Insulin Resistance Pathology of Diabetes: Atherosclerosis Neuropathy Susceptibility to Infection Pharmacological Prevention: Type I- Insulin Replacement Regimens Type II- Insulin Secretogogues - Insulin Sensitizers Pharmacological Treatment: examples: Viagra & Erectile Dysfunction Aldose Reductase Inhibitors & Neuropathy Insulin Sensitizers & Polycystic Ovary Syndrome

7. Atherosclerosis: Abnormal vascular smooth muscle migration to sub-endothelial space and proliferation Key abnormalities: - smooth muscle - lipid Significance: -↓ perfusion - infarction

9. Atherosclerosis Insult to Endothelium potential mechanisms include non-enzymatic glycosylation & lipid-induced macrophage growth factors Consequence & Focus for FIS Discussion: -defective inhibitory proteoglycans of endothelial extracellular matrix in contact with smooth muscle cells -deficient release of inhibitory NO to smooth muscle cells -abnormal smooth muscle migration & proliferation

10. Diabetic Neuropathy

11. mechanism for diabetes-induced neurodegeneration Sorbitol glucose → sorbitol → fructose –osmotic perturbations due to sorbitol (hydroxyated glucose), »“trapped” intracellularly »specific to neurons (aldose reductase) »elevated intraneuronally in diabetes due to hyperglycemia & insulin-independent neuronal glucose uptake – oxidative stress due to depletion in NADPH by aldose reductase

12. Diabetes & Neuropathy: 4 Journal Clubs 1)Descriptive changes: Diabetes-induced changes in morphology & electrophysiology 2)Causal role of sorbitol: Diabetes-induced intra-neuronal sorbitol, potentially leading to perturbations via osmotic distortion &/or oxidative stress 3)Abnormal protein phosphorylation of neuronal structure: Diabetes-induced abnormal neurophilament phosphorylation, potentially leading to impaired structural/functional integrity and ultimately ↓ conduction & terminal degeneration. 4)Loss of neurotransmitter synthesis in nerve terminal: Diabetes-induced degeneration of nitrergic neurons, specifically loss of NO synthesis, potentially leading to impaired vasodilation & erectile dysfuction

13. Diabetes & Immunology/Bacterial Pathogenesis Etiology of Type I diabetes: –Autoimmune destruction of β-cell Infections & diabetes –sensation (neural) –perfusion (vascular) –substrate for bacterial growth –host defense

14. Version date: 2006 FIS Final Exam: Sample Questions Q: Contrast the etiologies of Type I & Type II diabetes. (Basis for Answer: Type I- Autoimmune & Type II- Insulin Resistance) Q: Discuss the mechanisms for the potential pathological changes in a specific organ system, secondary to long-standing hyperglycemia and/or hyperlipidemia of Type II diabetes. (Basis for Answer: Erectile Dysfunction due to both vascular occlusion (atherosclerosis) & deficient NO release from neurons responsible for vasodilation Q: Review the pharmacological basis, including mechanism of action, for a prophylaxis and amelioration of this specific organ system disease - or its consequences. (Basis for Answer: Prophylaxis- insulin sensitizing drugs; Treatment- Viagra, a cyclic GMP phosphodiesterase inhibitor)