Regulation of Blood Glucose Level

Dr. Shabeena Patel

What goes wrong when the concentration decreases?

HypoglycaemiaThe symptoms associated

with low blood sugar are:

tiredness, confusion, dizziness, headaches, mood swings, muscle weakness, tremors, irreversible CNS damage, coma, death

What goes wrong when the concentration increases too far?

HyperglycaemiaThe symptoms include: Excessive thirst; frequent urination; fatigue; unexplained weight loss; vision problems, such as blurring; increased susceptibility to infections Dibetes mellitus

We eat food containing carbohydrates

Fundamental regulation / Autoregulation

• Hormones: • Insulin• Glucagon

Organs: Liver Skeletal muscles Pancreas Adipose tissue

ROLE OF

LIVER

Role of liver and Sk muscle

Role of the Pancreas

1. Digestion – secretes digestive enzymes2. Metabolism

• Regulation • Carbohydrates• Lipids• Proteins

• Produces primary messengers (hormones)• Insulin• Glucagon

Role of adipose tissue

Organ Glucose transporter Classification

Brain GLUT1 Glucose dependent

Erythrocyte GLUT1 Glucose dependent

Adipocyte GLUT4 Insulin dependent

Muscle GLUT4 Insulin dependent

Liver GLUT2 Glucose sensor

GK - cell GLUT2 Glucose sensor

Gut GLUT3-symporter ---- Sodium dependent

Kidney GLUT3-symporter ---- Sodium dependent

Glucose transporters

• 51 amino acids• 2 chains linked by disulfide bonds• 5800 Dalton molecular weight

MECHANISM OF INSULIN SECRETION

Mechanism of insulin action

ADIPOSE TISSUE AND

MUSCLES

insulin stimulates the synthesis of an enzyme (glucokinase) (low affinity to glucose) [ in the liver]• Required to ‘trap’ glucose in the cell (only when glucose concentration is high)

Insulin Control

Muscle Glucose uptake Glycogen synthesis

Liver Glucose uptake­ Glycogen synthesis­ Fatty acid synthesis¯ Glucose synthesis

BrainNo effect

PancreasBeta cells

Gastrointestinalhormones

Feedback

amino acids

glucose

triglyceridesAdipose­ Glucose uptake­ Glycerol production¯ Triglyceride breakdown Triglyceride synthesis Insulin

Most Cells Protein synthesis

Amino acids

Bloodglucose

Glucagon Control

Liver Glycogen breakdown­ Glucose synthesis Glucose release

BrainNo effect

PancreasAlpha cells

Exercise

Feedback

Adipose­ Triglyceride breakdown¯ Triglyceride storage

Blood glucose

Fatty acids

Epinephrine(stress)

Amino acids

Glucocorticoids• 1)Increase blood glucose:• i) Peripheral tissues :increase protein catabolism• Decrease uptake and utilization of glucose• ii)Liver : Increase amino acid uptake• Increase the transaminase activity• Increase gluconeogenesis• + Pyruvate carboxylase• + PEP carboxykinase• + Fructose -1,6-biphosphatase• +Glucose-6- phosphatase

• 2)Liver: Increase liver glycogen• + glycogen synthase activity

Glucocorticoids are catabolic to the peripheral tissues but anabolic to the liver

+ ACTH synthesis

Glucocorticoid syn

Anterior pituitary hormones

• 1)Growth hormone:• i)Decreases glucose uptake in tissues• ii)Increase liver gluconeogenesis• Chronic administration may lead to diabetes

mellitus due to stimulation and exhaution of beta cells

• 2)ACTH: Stimulates glucocorticoids synthesis

• Raise blood glucose level

Thyroid hormones

• Raise blood glucose levels• i)Increase hepatic glycogenolysis• ii)Increase sensitivity of tissues to catecholamines• iii)Increases destruction of insulin• iv) Increase absorption of hexoses from intestine• v) Increase peripheral tissue protein catabolism

Adipose tissue as endocrine gland

Plasma glucose level

Causes of hyperglycemia

• 1)Diabetes mellitus• 2)Hyperactivity of thyroid, pituitary and

adrenals• 3)Emotional stress• 4)diffuse pancreatic diseases• 5)Sepsis• 6)Asphyxia

Hypoglycemia

• 1)Overdosage of insulin • 2)Insulinoma• 3)Hypoactivity of thyroids –myxodema,cretinism• Pituitary gland• Adrenals- Addisons disease• 4)Severe liver diseases• 5)Glycogen storage diseases