Endocrine pancreas in insulin receptor-deficient mouse pups.
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.
Department of Genetics, Development and Molecular Pathology, ICGM, Institut National de la Santé et de la Recherche Médicale Unit 257, Paris, France.
M
M
Jackerott
A
A
Baudry
B
B
Lamothe
D
D
Bucchini
J
J
Jami
R L
RL
Joshi
D000818:Animals; D000831:Animals, Newborn; D005260:Female; D015870:Gene Expression; D005838:Genotype; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D005941:Glucokinase / Q000235:genetics; D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D006946:Hyperinsulinism / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D010191:Pancreatic Polypeptide / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011972:Receptor, Insulin / Q000172:deficiency / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics
D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D005941:Glucokinase; D011972:Receptor, Insulin