diabetes mellitus at a molecular level

Diabetes MellitusType 1 & Type 2

Ahmad Jabar Bawan BakrSarmad Awat

Contents

• Introduction•Normal State•Diabetes type 1 & 2• Symptoms & complications•Diagnosis & treatment

Introduction

•Diabetes is a group of metabolic disorders, resulting in hyperglycemia, due to defects in insulin secretion, insulin action, or both.•Diabetes Mellitus = DM = Diabetes•Diabetes = siphon (Greek) = a lot of urine is made•Mellitus = mel (Latin) = honey = the urine is sweet

Introduction

Introduction

Introduction

Blue Circle for Diabetes

Normal State

• Insulin and glucagon are two peptide hormones produced by the pancreas that regulate blood sugar level, homeostasis.•Homeostasis: body’s tendency to maintain relatively constant internal conditions.

Pancreas

• Pancreas has alpha cells () and beta cells (). Together they form Islets of Langerhans.

• Insulin is secreted by the beta cells of the pancreas, and glucagon is secreted by the alpha cells.

Homeostasis

• Insulin lowers down the blood sugar level when it is high (after meals), and glucagon rises the level when it is low (before meals).• Insulin takes the excess sugar into cells for energy or to the liver for storage.•Glucagon takes sugar from the liver and put it back to the blood.• As a result, the blood glucose level is kept nearly constant.

What happens to food after eating?

•During and immediately after a meal, digestion breaks carbohydrates down into sugar molecules, especially glucose.

• If fuel is to cars, glucose is to cells.• Cells need glucose to generate energy in the form of ATP, cellular respiration.

What happens to glucose?

• In the intestine, glucose is absorbed into the bloodstream via SGLT1 (secondary active transport) and GLUT2 (facilitated

diffusion) transmembrane proteins.

• The blood glucose level rises.

How is insulin released?

How is insulin released?

• Glucose enters beta cells of the pancreas by facilitated diffusion through the GLUT2 transmembrane proteins, down its concentration gradient.• Through cellular respiration, ATP is

generated from the glucose.• Rise in ATP closes the ATP-sensitive K+

channels, leading to depolarization.• Depolarization opens the voltage-

dependent Ca2+ channels, leading to entry of Ca2+ ions into the cell.• This causes vesicles containing insulin to

move to and fuse with the cell membrane and release insulin by exocytosis.

Why is insulin important?

•Most cells in the body are strongly influenced by insulin.• These cells don’t have GLUT2 on their membranes, so they can’t receive glucose directly.• Instead, They have GLUT4 which is another type of glucose-transporting protein.•GLUT4 can’t take glucose into the cell on its own. It requires a mechanism in which insulin plays an important role.

Action of Insulin

• ENPP1 (insulin receptor protein) receives insulin on the cell membrane and puts it into the cell.• IRS protein takes the insulin from ENPP1 and phosphorylates it.•GLUT4 receives glucose and puts it into the cell after it has bound the phosphorylated insulin.•Glucose is either used for energy through cellular respiration in the mitochondria, or stored as glycogen.

Action of Insulin

Kidneys

Kidneys

• In the S1 segment of the nephrons, SGLT2 reabsorbs 90% of all filtered glucose.• In the S3 segment of the nephrons, SGLT1 reabsorbs the remaining filtered glucose.

Diabetes

• In diabetes, the body is unable to maintain homeostasis of blood glucose levels. Glucose doesn’t enter cells, resulting in hyperglycemia.• Type 1 diabetes is characterized by the loss or decreased production of insulin hormone, insulin-dependent.• Type 2 diabetes is characterized by insensitivity to insulin (insulin resistance), non-insulin-dependent.

Diabetes

Types of Diabetes

Type 1• About 15% of all cases.•Most often found in under 40s.•Most common type found in childhood.

Type 2•About 85% of

all cases.•Most often

found in over 40s.

•Rarely found in childhood.

Causes of Type 1 Diabetes

Causes of Type 2 Diabetes

Symptoms

•Polydipsia (excessive thirst) from dehydration

•Polyuria (frequent urination)

Symptoms

•Polyphagia (excessive hunger)

• Fatigue (excessive tiredness)

Symptoms

•Weight loss

•Other symptoms from complications

Complications

• Diabetes is a disease characterized by hyperglycemia, but hyperglycemia leads to other diseases. This is known as the complications of diabetes.• Some effects of hyperglycemia happen over a short period of time and are more serious (acute complications).• Some other effects of hyperglycemia happen over a long period of time and are less serious (chronic complications).

Acute Complications

•Diabetic Ketoacidosis (DKA)•Hyperosmolar hyperglycemic non-ketotic syndrome (HHNS)

DKA

DKA

HHNS

HHNS

Chronic Complications

•Damage to small blood vessels (microvascular disease), causing malfunction of some organs like the eyes (blurriness and blindness).

•Damage to large blood vessels (macrovascular disease), leading to heart disease, poor blood flow, stroke and slow healing.

Chronic Complications

•Damage to the nerves (neuropathies), leading to many disorders including: numbness and tingling in the hands or feet, reduced sensation, irritability, nervousness, shakiness and confusion.

Diagnosis

Fasting blood glucose testThe test should be done after an overnight fast of 8 – 10 hours.

Fasting blood glucose (mg/dL)

Diagnosis

Below 110 Normal

Between 110 and 126 Pre-diabetes

Above 126 Diabetes

Treatment of type 1

• Insulin therapy• Injections under the skin several times each

day

• Insulin pump

Treatment of type 1

• Blood glucose monitoring• Glucometer

Treatment of type 2

•Healthy diet• Exercise•Medications

References

•www.slideshare.net/sararavi9/diabetes-mellitus-41789085•www.idf.org - International Diabetes Federation•www.ciencianews.com.br - Science and Technology Academy• science.csustan.edu/stone/chem4400/SJBR/DaSilveiraDaniel.pdf•Wikipedia•YouTube and Google Images