1. Safe induction of diabetes by high-dose streptozotocin in pigs
- Author
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Hidetaka, Hara, Yih Jyh, Lin, Xiaocheng, Zhu, Hao-Chih, Tai, Mohamed, Ezzelarab, A N, Balamurugan, A N, Balamarugan, Rita, Bottino, Stuart L, Houser, and David K C, Cooper
- Subjects
Blood Glucose ,medicine.medical_specialty ,endocrine system diseases ,Swine ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Body weight ,Streptozocin ,Diabetes Mellitus, Experimental ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Medicine ,Animals ,Humans ,Insulin ,Pancreas ,Glucose tolerance test ,Hepatology ,Insulin blood ,medicine.diagnostic_test ,C-Peptide ,business.industry ,Body Weight ,nutritional and metabolic diseases ,Fasting ,Glucose Tolerance Test ,medicine.disease ,Streptozotocin ,humanities ,Pancreatectomy ,Experimental pathology ,Female ,business ,medicine.drug - Abstract
Streptozotocin (STZ) has been widely used to induce diabetes in rodents and nonhuman primates, but it has been found difficult to achieve a completely diabetic state in pigs in the absence of detrimental side effects. As a result, pancreatectomy has been advocated in this species. We have investigated the effects of 2 dosages of STZ to safely induce diabetes in pigs.Three pigs received Zanosar STZ at 150 mg/kg (group 1). Four pigs received Zanosar STZ at 200 mg/kg (group 2). The levels of glucose, insulin, and C-peptide when (a) fasting, (b) 30 minutes after eating, and (c) during intravenous glucose tolerance tests (IVGTTs) were measured in all pigs for 4 weeks after STZ injection. To confirm how long the diabetic state can be maintained after induction with STZ, levels were measured for 20 weeks in group 2.One to 4 weeks after STZ administration, in group 1 (150 mg/kg) pigs, insulin and C-peptide levels were detected up to 7 microIU/mL and 0.4 ng/mL, respectively, both when fasting and after a meal test or IVGTT, indicating that the pigs had failed to become fully diabetic. In group 2 (200 mg/kg) pigs, insulin and C-peptide levels were less than the 2 microIU/mL and 0.25 ng/mL respective detection levels and did not increase after a meal test or IVGTT. Group 2 remained completely diabetic for the entire 20-week period of follow-up, without STZ-related hepatic or renal dysfunction.High-dose (200 mg/kg) Zanosar STZ induces diabetes safely and completely in pigs without side effects. Pancreatectomy can, therefore, be avoided.
- Published
- 2008