Mild streptozotocin diabetes in the Göttingen minipig. A novel model of moderate insulin deficiency and diabetes

Am J Physiol Endocrinol Metab. 2002 Jun;282(6):E1342-51. doi: 10.1152/ajpendo.00564.2001.

Abstract

Nonrodent models of diabetes are needed for practical and physiological reasons. Induction of mild insulin-deficient diabetes was investigated in male Göttingen minipigs by use of streptozotocin (STZ) alone (75, 100, and 125 mg/kg) or 125 mg/kg combined with pretreatment with nicotinamide (NIA; 0, 20, 67, 100, 150, and 230 mg/kg). Use of NIA resulted in a less steep slope of the regression line between fasting plasma glucose and changing doses compared with STZ [-7.0 +/- 1.4 vs. 29.7 +/- 7.0 mM. mg(-1). kg(-1), P < 0.0001]. Intermediate NIA doses induced moderate changes of glucose tolerance [glucose area under the curve increased from 940 +/- 175 to 1,598 +/- 462 mM. min, P < 0.001 (100 mg/kg) and from 890 +/- 109 to 1,669 +/- 691 mM. min, P = 0.003 (67 mg/kg)] with reduced insulin secretion [1,248 +/- 602 pM. min after 16 days and 1,566 +/- 190 pM. min after 60 days vs. 3,251 +/- 804 pM. min in normal animals (P < 0.001)] and beta-cell mass [5.5 +/- 1.4 mg/kg after 27 days and 7.9 +/- 4.1 mg/kg after 60 days vs. 17.7 +/- 4.7 mg/kg in normal animals (P = 0.009)]. The combination of NIA and STZ provided a model characterized by fasting and especially postprandial hyperglycemia and reduced, but maintained, insulin secretion and beta-cell mass. This model holds promise as an important tool for studying the pathophysiology of diabetes and development of new pharmacological agents for treatment of the disease.

MeSH terms

  • Animals
  • Arginine
  • Blood Glucose / analysis
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Disease Models, Animal*
  • Fasting
  • Food
  • Glucagon / blood
  • Glucose Tolerance Test
  • Insulin / blood
  • Insulin / deficiency*
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / pathology
  • Islets of Langerhans / physiopathology
  • Male
  • Niacinamide / administration & dosage
  • Streptozocin / administration & dosage
  • Swine, Miniature
  • Time Factors

Substances

  • Blood Glucose
  • Insulin
  • Niacinamide
  • Streptozocin
  • Glucagon
  • Arginine