1

Diabetes Mellitus

Dr. Othman Al-ShboulDepartment of Physiology

الرحيم الرحمن الله بسم

2

Pancreas• Pancreas is a mixed organ; having both endocrine and

exocrine portions• Endocrine portion: islets of pancreas: secreting hormones• Exocrine portion: secreting enzymes into the intestine

Exocrine portion of pancreas(acinar & duct cells)

3

Islets of Langerhans

Glucagon

Insulin

Somatostatin

Exocrine portion

4

Insulin

5

Insulin secretion is associated with energy abundance

Energy-giving foods in the diet, especially excess amounts of carbohydrates increases insulin secretion

Insulin affects carbohydrate, fat, and protein metabolism

6

Actions of Insulin

7

Actions on carbohydrates

o Facilitates glucose transport into most cells

o Stimulates glycogenesis (Glucose Glycogen)

o Inhibits glycogenolysis (Glycogen Glucose)

o Inhibits gluconeogenesis (aa. Glucose)

8

Glucose transport between the blood and cells

Glucose transporter (GLUT), Six forms (GLUT1-GLUT6)

Most important GLUT4 (skeletal muscle and adipose tissue cells)

GLUT4 is present on cell membrane upon insulin secretion only

Brain does not depend on insulin

Although skeletal muscles have GLUT4:

Resting depend on insulin Exercising no need for insulin, good for DM

9

Actions on fat

Enhances the entry of fatty acids from the blood into adipose tissue cells

Enhances transport of glucose into adipose tissue cells

Stimulates triglyceride synthesis

Inhibits lipolysis

Augments removal of fatty acids and glucose from the blood and promotes their storage in adipose tissue as triglycerides

10

Actions on protein

Promotes the active transport of amino acids from the blood into muscles and other tissues

Stimulates cells’ protein-synthesizing machinery

Inhibits protein degradation

Lowers blood amino-acid levels and enhances protein synthesis

11

Insulin vs. Glucagon

Glucose Glycogen

Insulin

Glucagon

12

Diabetes Mellitus

13

Diabetes Mellitus

A syndrome of impaired carbohydrate, fat, and protein metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to insulin.

14

Types of Diabetes Mellitus

Type I diabetes, or insulin-dependent diabetes mellitus (IDDM), 5-10%

Caused by lack of insulin secretion.

Type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM),

Caused by decreased sensitivity of target tissues to the metabolic effect of insulin (insulin resistance).

15

Type I Diabetes-Deficiency of Insulin Production by β-Cells of the Pancreas

5-10 % of diabetics

Disease/injury to the beta cells of the pancreas (viral infections or autoimmune disorders, heredity)

Hypoinsulinemia (↓insulin levels)

Can occur at any age, mostly teenagers-juvenile diabetes mellitus

Develop abruptly or over a period of time

Ketoacidosis (↑ketones in blood)

16

Complications of Diabetes Mellitus

1. High Blood Glucose Concentration (hyperglycemia)

Loss of Glucose in the Urine When [blood glucose] is above 180 mg/100 ml (blood

"threshold" for the appearance of glucose in the urine)

Glucose draws water into the urine by osmosis (osmotic diuresis)

polyuria (excessive urine excretion)

Dehydration (leading to polydipsia)

17

Complications of Diabetes Mellitus

18

1. High Blood Glucose Concentration (hyperglycemia)

Tissue Injury

capillary endothelial cells in the retina, mesangial cells in the renal glomerulus, and neurons and Schwann cells in peripheral nerves

glucose transport rate in these cells does not decline rapidly as a result of hyperglycemia, leading to high glucose inside the cell

retinopathy, neuropathy, nephropathy.

19

1. High Blood Glucose Concentration (hyperglycemia)

Tissue Injury

Blood vessels abnormalities inadequate blood supply to the tissues (hypoxia).

• Risk for heart attack, stroke • End-stage kidney disease (nephropathy)• Retinopathy affecting vision ??blindness• ischemia and gangrene of the limb

20

1. High Blood Glucose Concentration (hyperglycemia)

Tissue Injury

Peripheral neuropathy• e.g., decreased sensation in the extremities, the

most frequent complication of long-term diabetes• pain & symptoms in the legs and feet• erectile failure (neurogenic impotence in the

diabetic) Hypertension, secondary to renal injury Atherosclerosis, secondary to abnormal lipid metabolism

21

2. Increased Utilization of Fats and Metabolic Acidosis

o Increased the release of keto acids, such as acetoacetic acid and β hydroxybutyric acid, into the plasma leading metabolic acidosis

o Cholesterol generation and deposition

22

3. Diabetes Causes Depletion of the Body's Proteins

Rapid weight loss and asthenia (lack of energy) despite eating large amounts of food (polyphagia)

23

Type II Diabetes-Resistance to the Metabolic Effects of Insulin

90-95 % of all cases of diabetes mellitus

After age 30, adult-onset diabetes

Develops gradually

The most important risk factor for type II diabetes is obesity

Insulin secretion is normal or increased

Ketoacidosis: rare

24

Types of Diabetes Mellitus

25

Diagnosis of Diabetes Mellitus

Urine Glucose Level

Fasting Blood Glucose and Insulin Levels Normal fasting blood glucose level in the early morning:

80 to 90 mg/100 ml,

26

Glucose Tolerance Test

When a normal, fasting person ingests 1 gram of glucose per kilogram of body weight, the blood glucose level rises from about 90 mg/100 ml to 120 to 140 mg/100 ml and falls back to below normal in about 2 hours.

greater than normal rise in blood glucose level

Delayed return to control value

27

Acetone Breath

Breath

28

The END