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Related Concept Videos

Cells and Secretions of the Pancreas01:16

Cells and Secretions of the Pancreas

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The pancreas, a vital organ within the abdominal cavity, plays dual roles in the digestive and endocrine systems, collaborating with exocrine and endocrine cells to maintain optimal digestion and blood sugar levels.
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
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Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Adrenergic Receptors (Adrenoceptors): Classification01:27

Adrenergic Receptors (Adrenoceptors): Classification

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Adrenergic receptors, or adrenoceptors, respond to the autonomic neurotransmitter noradrenaline and other endogenous catecholamine agonists. They are classified into two main families, α and β, based on their pharmacological response and are further subdivided depending on their location, elicited response, and affinity to specific agonists or antagonists.
α-Adrenoceptors
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Adrenergic Receptors: β Subtype01:26

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β-adrenoceptors have varied sensitivities towards adrenaline, noradrenaline, and isoprenaline. The order of agonist potency is as follows:
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Insulin: The Receptor and Signaling Pathways01:28

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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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Spare Receptors01:30

Spare Receptors

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Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
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Adrenoceptor Expression and Function in the Endocrine Pancreas.

Haneen Dwaib1, Martin C Michel2

  • 1Department of Clinical Nutrition and Dietetics, Palestine Ahliya University, Bethlehem, Palestine. Haneen.dwaib@paluniv.edu.ps.

Handbook of Experimental Pharmacology
|June 13, 2024
PubMed
Summary

The alpha2A-adrenoceptor (α2A-AR) in pancreatic beta cells inhibits insulin release, potentially contributing to type 2 diabetes. Targeting this receptor shows limited therapeutic success.

Keywords:
DiabetesGlucagon releaseInsulinPancreasα2-Adrenoceptorβ-Adrenoceptor

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Area of Science:

  • Endocrinology
  • Neuroscience
  • Pharmacology

Background:

  • The sympathetic nervous system regulates pancreatic endocrine function, particularly insulin release.
  • Alpha2A-adrenoceptors (α2A-AR) are highly expressed in the human pancreas and mediate sympathetic inhibition of insulin secretion.
  • Increased α2A-AR signaling is linked to type 2 diabetes risk.

Purpose of the Study:

  • To investigate the role of α2A-AR in pancreatic beta cell function and its potential as a therapeutic target for type 2 diabetes.
  • To evaluate the clinical efficacy of targeting α2A-AR for diabetes treatment.

Main Methods:

  • Review of studies on α2-AR and β-AR effects on insulin secretion.
  • Analysis of α2A-AR polymorphism association with diabetes risk.
  • Examination of clinical trial data for α2A-AR-targeting drugs.

Main Results:

  • α2A-AR activation inhibits insulin secretion, while antagonists increase it, suggesting physiological relevance.
  • A specific α2A-AR polymorphism correlates with elevated diabetes risk.
  • Clinical trials targeting α2A-AR for type 2 diabetes have shown limited efficacy.

Conclusions:

  • While α2A-AR signaling in pancreatic beta cells is physiologically significant and linked to diabetes, it has limited therapeutic relevance due to low drug efficacy.
  • Further research may explore alternative therapeutic strategies for managing insulin secretion in diabetes.