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F.7 Biology

Individual Summer Project on Diabetes

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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)

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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

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Mechanism of insulin action and diabetes

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Post – prandial deposit of glucose 1

G

G

G

G

Inte

stin

e lu

men

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

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Post – prandial deposit of glucose 2

Glucos

e

Blood Glucose

Glucose

Glycogen a.a protein

Muscle

Glut 4Kidney

FA

Glycerol TG

Adipocyte

Glut 4

Brain

Glucose

Glucose

FA

Intestine

Liver

Glycogen

GlucoseFA TG

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Glucose Transporter

G G

Glucose Transporter

CellPlasma membrane

Glucose molecule

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Insulin stimulates Glut4 – mediated glucose transport

G

G

GG

GG G

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

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Defective insulin function in diabetes

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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

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Mechanism of Type I diabetes

Immune system cannot recognizeβcells → cause destruction ofβcells → no insulin producedThus increase the blood glucose levelCan control by injecting insulin into blood

Why don’t have oral medicine of insulin?

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Insulin deficiency causes type I diabetes

Glucos

e

Blood Glucose

Glucose

Glycogen a.a protein

Muscle

Glut 4

Kidney

FA

Glycerol TG

Adipocyte

Brain

Glucose

Glucose

FA

Intestine

Liver

Glycogen

GlucoseFA TG

Glut 4

Insulin

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Mechanism of Type II diabetes

G

G

GG

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

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Abnormal glucose deposit in type II diabetes

Glucos

e

Blood Glucose

Glucose

Glycogen a.a protein

Muscle

Glut 4

Kidney

FA

Glycerol TG

Adipocyte

Brain

Glucose

Glucose

FA

Intestine

Liver

Glycogen

GlucoseFA TG

Glut 4

Insulin

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Symptoms of diabetes

Few glucose can reach muscle cellWeak and fatigueBreakdown protein to release energy Feels hungry, loss weight Kidney extract excess glucoseThirsty, frequent urination, kidney damage

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Complications of diabetes

Skin problemsHeart disease and stroke (Cardiovascular disease)Nerve damageFoot ulcerVision problemsKidney disease

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Risk factors of diabetes

Family history of diabetesAfrican 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

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Diagnosis of diabetes

Fasting plasma glucose test:- measures blood sugar after a 12 to 14

hour fast Normal : 70 – 110 mg / dlDiabetes: >126 mg / dl on two or more

tests on different days

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Diagnosis of diabetes

Random plasma glucose test:- It can be done at any timeDiabetes: > 200 mg / dl (other tests needed)

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Diagnosis of diabetes

Oral glucose tolerance test (OGTT)

8- 16 hours before Start fastingFasting plasma glucose test

0 min 75 g of glucose in 300 ml of water is given to the person orally within 5 minutes

30,60,90,120 min Draw blood to measure blood glucose

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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

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Urine Test

Always a high concentration of blood glucose

Results in the presence of glucose in urineCells cannot utilize glucose- Switch energy source to fatty acid- Produce acetyl – CoA and thus ketones pro

duced (Acetoacetate and acetone) Ketonuria

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Urine Analysis

Ancient trick: Technique of pouring urine on the ground and observing whether it attracts insects

1673 Willis: Sweet taste of diabetic urine1790 Home: Yeast fermentation1841 Trommer: Alkaline copper reduction1911 Benedict: Alkaline copper reduction (First stable, practical liquid test of urine sugar)

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Urine Analysis

Now: Multistix Simple Multi – purpose Fast Reasonable accurate Each square is embedd

ed with enzyme or chemical that react with urine biomolecules

Reaction result in colour change

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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)

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Control of diabetes

Weight lossStay physically activeStay with a balanced dietGlucose – lowering medicationInsulin injection

(For Type I and end state of Type II)