1. 2003/8/31 1 F.7 Biology Individual Summer Project on Diabetes

2. 2003/8/312 What is diabetes? Diabetes is a group of metabolic diseases characterized by hyperglycemia leading to long term complications There are two major types of diabetes: - Type 1: Juvenile onset, insulin dependent (IDDM) - Type 2: Maturity onset, insulin independent (NIDDM)

3. 2003/8/313 Why study diabetes? Approximately 17 million people in the US (6.2 % of the population) have diabetes Total medical costs spent on diabetes approaches 100 billions every year Estimated China will contribute to 38 million cases of diabetes by year 2025

4. 2003/8/31 4 Mechanism of insulin action and diabetes

5. 2003/8/315 Post – prandial deposit of glucose 1 G G G Intestine lumen Carbohydrate intake G G G Increased in blood glucose level G β cells Pancreas Insulin secretion increase 1 2 3 4 G = Glucose = Glucose transporters

6. 2003/8/316 Post – prandial deposit of glucose 2 Glucose Blood Glucose Glucose Glycogen a.a protein Muscle Glut 4 Kidney FA Glycerol TG Adipocyte Glut 4 Brain Glucose FA Intestine Liver Glycogen Glucose FA TG

7. 2003/8/317 Glucose Transporter GG Cell Plasma membrane Glucose molecule

8. 2003/8/318 Insulin stimulates Glut4 – mediated glucose transport G G G G GGG Insulin Insulin receptor Glut 4 Vesicle 1.Insulin binding to insulin receptors (IR) 2.IR transmits signals  movement of Glut 4 containing vesicles towards the cell membrane 3.Fusion of Glut 4 containing vesicles to cell membrane 4.Increase glucose influx 1 2 3 4

9. 2003/8/31 9 Defective insulin function in diabetes

10. 2003/8/3110 Mechanism of Type I and Type II diabetes Type I Type II Pancreas Defective pancreatic βcell insulin secretion due to βcell damage Cause: Autoimmune mechanism Adipocytes Muscle Insulin resistance Cause: Multifactorial

11. 2003/8/3111 Mechanism of Type I diabetes Immune system cannot recognizeβcells → cause destruction ofβcells → no insulin produced Thus increase the blood glucose level Can control by injecting insulin into blood Why don’t have oral medicine of insulin?

12. 2003/8/3112 Insulin deficiency causes type I diabetes Glucose Blood Glucose Glucose Glycogen a.a protein Muscle Glut 4 Kidney FA Glycerol TG Adipocyte Brain Glucose FA Intestine Liver Glycogen Glucose FA TG Glut 4 Insulin

13. 2003/8/3113 Mechanism of Type II diabetes G G G G G Insulin Insulin receptor Glut 4 Vesicle 1.Insulin binding to insulin receptors (IR) 2.IR cannot transmits signals  No movement of Glut 4 containing vesicles towards the cell membrane 3.No fusion of Glut 4 containing vesicles to cell membrane 4.Decrease glucose influx 1 2 3 4

14. 2003/8/3114 Abnormal glucose deposit in type II diabetes Glucose Blood Glucose Glucose Glycogen a.a protein Muscle Glut 4 Kidney FA Glycerol TG Adipocyte Brain Glucose FA Intestine Liver Glycogen Glucose FA TG Glut 4 Insulin

15. 2003/8/3115 Symptoms of diabetes Few glucose can reach muscle cell  Weak and fatigue Breakdown protein to release energy  Feels hungry, loss weight Kidney extract excess glucose  Thirsty, frequent urination, kidney damage

16. 2003/8/3116 Complications of diabetes Skin problems Heart disease and stroke (Cardiovascular disease) Nerve damage Foot ulcer Vision problems Kidney disease

17. 2003/8/3117 Risk factors of diabetes Family history of diabetes African Americans, Latinos, Asian Americans, Native Americans and Pacific Islanders High blood pressure or very high blood cholesterol or triglyceride levels Obesity Older than 45 years of age

18. 2003/8/3118 Diagnosis of diabetes Fasting plasma glucose test: - measures blood sugar after a 12 to 14 hour fast Normal : 70 – 110 mg / dl Diabetes: >126 mg / dl on two or more tests on different days

19. 2003/8/3119 Diagnosis of diabetes Random plasma glucose test: - It can be done at any time Diabetes: > 200 mg / dl (other tests needed)

20. 2003/8/3120 Diagnosis of diabetes Oral glucose tolerance test (OGTT) 8- 16 hours beforeStart fasting Fasting plasma glucose test 0 min75 g of glucose in 300 ml of water is given to the person orally within 5 minutes 30,60,90,120 minDraw blood to measure blood glucose

21. 2003/8/3121 Diagnosis of diabetes Normal: 2 – hour glucose level <140 mg/dl and all values between 0 and 2 hours are < 200 mg/dl Diabetes: Two diagnostic tests done on different days showing high blood glucose level

22. 2003/8/3122 Urine Test Always a high concentration of blood glucose Results in the presence of glucose in urine Cells cannot utilize glucose - Switch energy source to fatty acid - Produce acetyl – CoA and thus ketones produced (Acetoacetate and acetone)  Ketonuria

23. 2003/8/3123 Urine Analysis Ancient trick: Technique of pouring urine on the ground and observing whether it attracts insects 1673 Willis: Sweet taste of diabetic urine 1790 Home: Yeast fermentation 1841 Trommer: Alkaline copper reduction 1911 Benedict: Alkaline copper reduction (First stable, practical liquid test of urine sugar)

24. 2003/8/3124 Urine Analysis Now: Multistix  Simple  Multi – purpose  Fast  Reasonable accurate  Each square is embedded with enzyme or chemical that react with urine biomolecules  Reaction result in colour change

25. 2003/8/3125 Determination of plasma Insulin level Enzyme linked Immunosorbent Assay (ELISA) Antigen: Insulin Antibody: Anti – insulin antibody Antibody conjugate: Anti – insulin monoclonal antibody conjugated to horseradish peroxidase (HRP) Substrate: 3,3’,5,5’- tetramethylbenzidine (TMB)

26. 2003/8/3126 Control of diabetes Weight loss Stay physically active Stay with a balanced diet Glucose – lowering medication Insulin injection (For Type I and end state of Type II)