Endocrine pancreas in insulin receptor-deficient mouse pups

Diabetes. 2001 Feb:50 Suppl 1:S146-9. doi: 10.2337/diabetes.50.2007.s146.

Abstract

Insulin receptor (IR)-deficient pups rapidly become hyperglycemic and hyperinsulinemic and die of diabetic ketoacidosis within a few days. Immunocytochemical analysis of the endocrine pancreas revealed that IR deficiency did not alter islet morphology or the number of beta-, alpha-, delta-, and pancreatic polypeptide (PP) cells. The lack of IR did not result in major changes in the expression of islet hormone genes or of beta-cell-specific marker genes encoding pancreas duodenum homeobox-containing transcription factor-1 (PDX-1), glucokinase (GCK), and GLUT2, as shown by reverse transcriptase-polymerase chain reaction analysis. The serum glucagon levels in IR-deficient and nondiabetic littermates were comparable. Finally, total insulin content in the pancreas of IR-deficient pups was gradually depleted, indicating sustained insulin secretion, not compensated for by increased insulin biosynthesis. These findings are discussed in light of recent results suggesting a role of IR in beta-cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Female
  • Gene Expression
  • Genotype
  • Glucagon / genetics
  • Glucagon / metabolism
  • Glucokinase / genetics
  • Glucose Transporter Type 2
  • Homeodomain Proteins*
  • Hyperinsulinism / genetics
  • Hyperinsulinism / metabolism
  • Immunohistochemistry
  • Insulin / genetics
  • Insulin / metabolism
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Mutant Strains
  • Monosaccharide Transport Proteins / genetics
  • Pancreatic Polypeptide / genetics
  • Pancreatic Polypeptide / metabolism
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Insulin / deficiency
  • Receptor, Insulin / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Somatostatin / genetics
  • Somatostatin / metabolism
  • Trans-Activators / genetics

Substances

  • Glucose Transporter Type 2
  • Homeodomain Proteins
  • Insulin
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Somatostatin
  • Pancreatic Polypeptide
  • Glucagon
  • Glucokinase
  • Receptor, Insulin