Hormonal control of energy metabolism

Hormonal Control of Energy Metabolism

Course Code: HUF2-110
Academic Year: 2025-26

Overview of Content

• Hormonal control of energy metabolism

  • List of hormones

  • Major target tissues

  • Metabolic processes

• Reasons for regulation

  • Fed/anabolic state

  • Fasting/catabolic state

• Body defense against hypoglycemia

  • Processes and hormones involved

  • Counter-regulatory hormone response to insulin-induced hypoglycemia (early/later response; synergistic interaction)

• Diabetes mellitus

  • Classification

  • Comparisons between type 1 and type 2 diabetes mellitus

  • Diagnostic criteria of diabetes and pre-diabetes

  • Proposed etiology of type 2 DM and deterioration of β-cell function

  • Molecular mechanism of insulin resistance

Hormones Involved

• Insulin

• Glucagon

• Epinephrine

• Cortisol

• Growth Hormone

Metbolic Processes Involved

• Glycogen synthesis

• Lipid synthesis

• Protein synthesis

• Glycogenolysis

• Gluconeogenesis

• Lipolysis

• Ketogenesis

• Proteolysis

Major Organs Involved

• Liver

• Adipose tissue

• Muscle

Summary of Normal Hormonal Influences on Metabolism

Effects of Hormones

• Insulin

  • Stimulates glucose uptake by cells.

  • Stimulates amino acid uptake by cells.

  • Stimulates glucose catabolism for energy.

  • Stimulates glycogenesis.

  • Stimulates lipogenesis and fat storage.

  • Inhibits gluconeogenesis.

  • Stimulates protein synthesis (anabolic).

• Glucagon

  • Stimulates glycogenolysis.

  • Stimulates lipolysis and fat mobilization.

  • Stimulates gluconeogenesis.

  • Stimulates protein breakdown (catabolic).

• Epinephrine

  • Similar effects to glucagon in increasing glucose production and mobilization of fats.

• Cortisol

  • Increases gluconeogenesis.

  • Increases proteolysis and lipolysis.

• Growth Hormone

  • Supports gluconeogenesis and promotes lipolysis.

Regulation of Energy Metabolism

Fed/Anabolic State

• Effects of Insulin:

  • Increase glucose and amino acid uptake.

  • Increase glycolysis (glucose utilization).

  • Increase glycogen synthesis in liver and muscle.

  • Increase lipogenesis in adipose tissue.

  • Increase protein synthesis in muscle.

  • Inhibition of catabolic processes.

Fasting/Catabolic State

• Hormonal Control:

  • Controlled by glucagon, epinephrine, GH, and cortisol.

• Energy Supply to the Body:

  • Origin of Fuel:

  • Liver: Glycogen, glucose, gluconeogenesis.

  • Muscle: Amino acids from muscle, lactate from RBCs.

  • Adipose tissue: Triglycerides, fatty acids, glycerol.

• Fuel Consumption:

  • Increase in glucose production through glycogenolysis and gluconeogenesis.

  • Decrease in glucose utilization by insulin-responsive tissues.

  • Increased lipolysis and ketogenesis for energy.

Body Defense Against Hypoglycemia

Counter-Regulatory Hormones

• Hormones that counter-regulate against the hypoglycemic effect of insulin.

• Types of Responses:

  • Some hormones respond early while others respond later, depending on the degree of hypoglycemia.

  • Actions include stimulating glycogenolysis, gluconeogenesis, and lipolysis.

Recommendations for Management of Hypoglycemia

• Intravenous infusion of glucose:

  • Dextrose solution.

• Injection of glucagon:

  • Stimulates glycogenolysis and gluconeogenesis.

• Oral intake of glucose:

  • Candy, fruit juice, or bananas.

Diabetes Mellitus

Classification

Diabetes Mellitus is characterized by:

• Hyperglycemia resulting from defects in insulin secretion, insulin action, or both.

Types:

1. Type 1 Diabetes Mellitus (T1DM):

   • Caused by an absolute deficiency of insulin due to β-cell destruction.

   • Previously referred to as insulin-dependent diabetes or juvenile-onset diabetes.

2. Type 2 Diabetes Mellitus (T2DM):

   • Caused by a combination of insulin resistance and a progressive loss of adequate β-cell insulin secretion.

   • Previously referred to as non-insulin dependent diabetes or adult-onset diabetes.

3. Specific Types of Diabetes:

   • Due to other causes or drug-induced (e.g., glucocorticoid use, GH excess).

4. Gestational Diabetes:

• Progression of T2DM:

  • Patients may undergo compensatory increase in insulin secretion prior to β-cell failure.

  • Eventually, may require insulin injections to maintain blood glucose levels.

Diagnosis of Diabetes Mellitus

• Symptoms:

  • Polyuria, polydipsia, unexplained weight loss.

• Diagnostic Criteria:

  • Fasting plasma glucose (FPG) levels ≥7.0 mmol/L.

  • 2-hour post 75 g OGTT plasma glucose ≥11.1 mmol/L.

  • Hemoglobin A1C >6.5%.

  • Random plasma glucose ≥11.1 mmol/L.

Proposed Etiology of Type 2 Diabetes Mellitus

• Obesity:

  • Especially visceral fat as a major contributing factor to insulin resistance via TNF-α, resistin, and free fatty acids (FFA).

  • Visceral fat influences hepatic metabolism directly through the hepatic portal circulation.

• Hyperinsulinemia's Role:

  • Developed in response to hyperglycemia, worsens insulin resistance through receptor downregulation and desensitization.

• Deterioration of β-cell Function:

  • Results from glucotoxicity and lipotoxicity (including oxidative stress and reactive oxygen species).

Molecular Mechanisms of Insulin Resistance

1. Decreased Insulin Receptors:

   • Loss in density or number due to cell size increase.

2. Lipid Accumulation:

   • High caloric intake leads to formation of lipotoxic precursors.

   • DAG activates PKC, which decreases insulin signaling efficiency.

3. Fatty Acyl-CoA Entry into Cells:

   • Causes inadequate cellular oxidation and lipid droplet accumulation, leading to further signaling interference.

Physiological Adaptation to Starvation

1. Metabolic Response:

   • Shift from carbohydrate to fat metabolism.

   • Initially depletes carbohydrate stores (glycogen).

2. Prolonged Starvation Effects:

   • Increase in ketogenesis and reliance on fat-derived fuels during extended periods without food.

References

• Starvation: Metabolic Changes.

• Dermatological changes and protein metabolism affected during prolonged starvation.

• Diabetes Classification: American Diabetes Association (ADA) standards.
  Note: Detailed citations and URLs of resources used in the material can be added as needed.