The Effect of Global SSTR5 Gene Ablation on the Endocrine Pancreas and Glucose Regulation in Aging Mice

J Surg Res. 2005 Nov;129(1):64-72. doi: 10.1016/j.jss.2005.05.024. Epub 2005 Jul 18.

Abstract

Introduction: The purpose of this study was to examine the effect of global gene ablation of SSTR5 on the endocrine pancreas, insulin secretion, and glucose tolerance in aging mice, as SSTR5 is a primary regulator of insulin secretion in the mouse pancreas.

Methods: Global SSTR5-/- mice were generated and genotypes were verified using Southern blot and RT-PCR. Glucose tolerance and in vivo insulin secretion in SSTR5-/- and WT mice were examined using intraperitoneal glucose tolerance test (IPGTT;1.2-2.0 mg/kg) at 3 and 12 months of age (n = 8 per group). Basal and glucose-stimulated insulin secretion in vitro was studied using the isolated perfused mouse pancreas model at 3 and 12 months. Pancreata were removed and levels of insulin, glucagon, somatostatin, and SSTR1 were studied using immunohistochemical analysis along with H&E staining of the pancreata.

Results: Genotyping verified the absence of SSTR5 in SSTR5-/- mice. IPGTT demonstrated that 3-month-old SSTR5-/- mice were glucose intolerant despite similar insulin secretion both in vivo and in vitro and enlarged islets. At 12 months of age, SSTR5-/- mice had basal hypoglycemia and improved glucose intolerance associated with hyperinsulinemia in vivo and in vitro and enlarged islets. SSTR5-/- mice had increased insulin clearance at 3 and 12 months of age. SSTR1 expression was significantly increased in islets at 3 months of age, but was nearly absent in islets at 12 months of age, as was somatostatin staining in SSTR5-/- mice.

Conclusions: These results suggest that both SSTR5 and SSTR1 play a pivotal role in insulin secretion and glucose regulation in mice and that their regulatory effects are age-related.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging*
  • Animals
  • Blood Glucose / metabolism
  • Body Weight
  • Female
  • Glucagon / analysis
  • Glucose / pharmacology*
  • Glucose Intolerance / genetics
  • Glucose Tolerance Test
  • Growth Disorders / genetics
  • Immunohistochemistry
  • Insulin / analysis
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Mice, Knockout
  • Receptors, Somatostatin / deficiency*
  • Receptors, Somatostatin / genetics*
  • Receptors, Somatostatin / physiology

Substances

  • Blood Glucose
  • Insulin
  • Receptors, Somatostatin
  • somatostatin receptor 5
  • Glucagon
  • Glucose