Pancreatic Islets: Insulin, Glucagon, and Somatostatin

Posted on Mar 19, 2025 in Human Nutrition and Dietetics

Pancreatic Endocrine Islets

Pancreatic endocrine islets, or islets of Langerhans, constitute approximately 1% of the pancreatic mass. They are innervated by the autonomic nervous system (ANS), feature intercellular communication, and possess a fine vascular network. Key hormones produced include insulin (β cells), glucagon (α cells), and somatostatin (δ cells).

Insulin Synthesis

Insulin synthesis begins with the ribosomal transcription of pre-proinsulin from mRNA. In the endoplasmic reticulum, pre-proinsulin folds via two disulfide bonds, forming proinsulin. Within the Golgi apparatus, proinsulin is cleaved by enzymes into equimolar amounts of insulin and C-peptide, which are then stored in membrane-bound granules.

Regulation of Insulin Secretion

Insulin secretion is regulated by multiple factors, including:

  • Stimuli: Glucose, amino acids (arginine, leucine), ketoacids, and fatty acids.
  • Autonomic Nervous System: Sympathetic (inhibitory) and parasympathetic (stimulatory) activity.
  • Hormones:
    • Enhancers: Glucagon, secretin, pancreozymin, gastric inhibitory peptide, acetylcholine.
    • Inhibitors: Gastrin, cholecystokinin, gastric inhibitory peptide, somatostatin.
  • Cell Signaling: Paracrine interactions.

The mechanism involves ATP-dependent closure of potassium channels, leading to membrane depolarization, calcium influx, and activation of protein kinase C. This triggers cytoskeletal changes involving myosin and contractile cilia, ultimately resulting in insulin exocytosis.

β cells are highly sensitive to small changes in glucose concentration. The insulin secretory response is biphasic:

  1. An initial rapid phase (approximately 10 minutes), likely due to the release of pre-formed insulin granules.
  2. A later, more sustained phase involving de novo insulin biosynthesis.

This biphasic response is crucial for maintaining glucose homeostasis.

Insulin Metabolism

Fasting insulin concentrations (measured by radioimmunoassay, RIA) are typically 5-15 μU/ml, rising to 30-75 μU/ml postprandially. C-peptide levels are 2-4 mg/ml postprandially, and can reach 4-6mg/ml. Insulin has a half-life of approximately 4.8 minutes, while proinsulin’s half-life is about 17.5 minutes. Insulin degradation occurs primarily in the liver and kidneys, whereas proinsulin and C-peptide are primarily degraded in the kidneys.

Insulin Receptor

The insulin receptor, composed of α and β subunits, is responsible for insulin recognition. These receptors are continuously degraded and resynthesized. Their concentration is *not* downregulated by insulin. Receptor affinity is reduced by catecholamines, glucagon, growth hormone, corticosteroids, estrogen, progesterone, and placental lactogen. The maximal effect of insulin is achieved with only 10% receptor occupancy.

Metabolic Effects of Pancreatic Hormones

Insulin

Insulin is an anabolic hormone that promotes energy storage and protein synthesis. It is also anti-catabolic, playing a key role in glucose homeostasis. Insulin affects the metabolism of amino acids, fatty acids, ketoacids, and lipoproteins.

  • Carbohydrate Metabolism: Insulin promotes glucose utilization in adipose tissue and muscle by increasing glucose transport. In the liver, it enhances oxygenation, glycogen storage, and inhibits gluconeogenesis (by reducing muscle catabolism).
  • Lipid Metabolism: Insulin promotes triglyceride synthesis and storage, inhibits lipolysis (reducing plasma free fatty acids and their delivery to the liver), reduces hepatic ketogenesis, and increases triglyceride synthesis.
  • Protein Metabolism: Insulin increases amino acid uptake by muscle, stimulates protein synthesis, and inhibits proteolysis.
  • Lipoprotein Effects: Insulin activates lipoprotein lipase, promoting lipoprotein catabolism and increasing high-density lipoprotein (HDL) levels.

Glucagon

Glucagon is a catabolic hormone that mobilizes energy substrates. It stimulates neoglucogenesis, glycogenolysis, lipolysis (releasing free fatty acids), and hepatic ketogenesis. Glucagon also promotes protein degradation, increasing amino acid availability for gluconeogenesis.

Somatostatin

Somatostatin modulates intestinal nutrient absorption and inhibits endocrine, exocrine, and motor functions of the digestive tract. It indirectly regulates insulin and glucagon secretion through an inhibitory effect.