Ontogeny of glucagon messenger RNA and encoded precursor in the rat intestine

S L Jin1, M A Hynes, P K Lund

  • 1Department of Physiology, School of Medicine, University of North Carolina, Chapel Hill 27599-7545.

Regulatory Peptides
|July 30, 1990
PubMed

Insights

Intestinal proglucagon gene expression begins around day 14 of fetal development in rats. A significant increase in L cell numbers between days 17 and 18 correlates with rising proglucagon mRNA levels.

Area of Science:

  • Developmental biology
  • Molecular endocrinology
  • Gastrointestinal physiology

Background:

  • Proglucagon is a key hormone precursor synthesized in intestinal L cells.
  • Understanding the regulation of proglucagon during development is crucial for metabolic research.

Purpose of the Study:

  • To investigate the ontogeny of proglucagon mRNA and its precursor in the developing rat intestine.
  • To identify the onset and developmental trajectory of intestinal proglucagon gene expression.

Main Methods:

  • Immunocytochemistry to detect proglucagon antigenic determinants.
  • In situ hybridization histochemistry to quantify proglucagon mRNA.
  • Analysis of L cell density during fetal gestation.

Main Results:

  • Proglucagon expression and mRNA translation were first detected at day 14 of fetal gestation (E14).
  • A significant 10-fold increase in intestinal L cell density occurred between E17 and E18.
  • Proglucagon mRNA abundance increased 8-fold between E17 and E18, correlating with L cell proliferation.

Conclusions:

  • Intestinal proglucagon gene expression initiates around E14 in rats.
  • The surge in proglucagon mRNA between E17-E18 is primarily attributed to an increase in L cell numbers.
  • This study provides insights into the developmental regulation of proglucagon in the gut.

Related Concept Videos

Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
Post-translational Translocation of Proteins to the RER01:27

Post-translational Translocation of Proteins to the RER

A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

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.
Insulin and C-peptide are co-secreted in...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

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 this inhibition is released...
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...