F.7 Biology

1. F.7 Biology Individual Summer Project on Diabetes

2. 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. 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. Mechanism of insulin action and diabetes

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

6. Post – prandial deposit of glucose 2 Brain Glucose Liver Glucose Glycogen Intestine TG FA Glucose FA Blood Glucose FAGlycerol TGAdipocyte Glut 4 Kidney Glucose Glut 4 GlucoseGlycogen a.a protein Muscle

7. Glucose Transporter G G Glucose molecule Glucose Transporter Plasma membrane Cell

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

9. Defective insulin function in diabetes

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

11. 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. Insulin deficiency causes type I diabetes Brain Glucose Liver Glucose Glycogen Intestine TG FA Glucose FA Blood Glucose FAGlycerol TGAdipocyte Kidney Glucose Insulin GlucoseGlycogen a.a protein Muscle Glut 4 Glut 4

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

14. Abnormal glucose deposit in type II diabetes Brain Glucose Liver Glucose Glycogen Intestine TG FA Glucose FA Blood Glucose FAGlycerol TGAdipocyte Kidney Glucose Insulin GlucoseGlycogen a.a protein Muscle Glut 4 Glut 4

15. 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. Complications of diabetes • Skin problems • Heart disease and stroke (Cardiovascular disease) • Nerve damage • Foot ulcer • Vision problems • Kidney disease

17. 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. 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. Diagnosis of diabetes • Random plasma glucose test: • It can be done at any time Diabetes: > 200 mg / dl (other tests needed)

20. Diagnosis of diabetes • Oral glucose tolerance test (OGTT)

21. 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. 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. 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. 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. 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. 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)