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

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

FIS 2006 (Diabetes)Version date: Aug 03, 2006

Final Exam: Integrative Perspective on Diabetes - 10% 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.

FIS Organization:

Exam #1- Basic Principles → diabetes

Exam #2- Neurobiology → diabetes

Exam #3- Endocrinology → diabetes

Exam #4- Immunology & Bacterial Pathogenesis → diabetes ↓

↓

(Exam #5: final)

FIS 2006 (Diabetes)

Lectures:

Sept 2 - Diabetes & PolyphagiaOct 06 - InsulinOct 10 - Counter Regulatory HormonesOct 18, 18 & 20 - Homeostasis & Responses to External EnvironmentNov 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 OrganizationSept 18 - Diabetes & Neuropathy Journal ClubSept 25 - Diabetes & Neuropathy Journal ClubOct 02 - Diabetes, Erectile Dysfunction & Viagra

Basic Principles & Endocrinology

Aug 28- Diabetes & AtherosclerosisOct 09 - Diabetes, Insulin Resistance & Metabolic SyndromeOct 16 – Pharmacological Management of DiabetesOct 23 - Diabetes, Insulin Resistance & Polycystic Ovary Syndrome

Immunology & Bacterial Pathogenesis:

Nov 27 - Immunology of DiabetesDec 04- Infections & Diabetes

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 DysfunctionAldose Reductase Inhibitors & NeuropathyInsulin Sensitizers & Polycystic Ovary Syndrome

Atherosclerosis: Abnormal vascular smooth muscle migration to sub-endothelial spaceand proliferation

Key abnormalities:- smooth muscle- lipid

Significance:-↓ perfusion- infarction

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

Diabetic Neuropathy

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

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

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

Version date: 2006FIS 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)