Safe induction of diabetes by high-dose streptozotocin in pigs

Hidetaka Hara, Yih-Jyh Lin, Xiaocheng Zhu, Hao Chih Tai, Mohamed Ezzelarab, A. N. Balamarugan, Rita Bottino, Stuart L. Houser, David K.C. Cooper

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

OBJECTIVES: 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. METHODS: 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. RESULTS: One to 4 weeks after STZ administration, in group 1 (150 mg/kg) pigs, insulin and C-peptide levels were detected up to 7 μIU/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 μIU/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. CONCLUSIONS: High-dose (200 mg/kg) Zanosar STZ induces diabetes safely and completely in pigs without side effects. Pancreatectomy can, therefore, be avoided.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalPancreas
Volume36
Issue number1
DOIs
Publication statusPublished - 2008 Jan 1

Fingerprint

Streptozocin
Swine
C-Peptide
Glucose Tolerance Test
Pancreatectomy
Insulin
Meals
Fasting
Experimental Diabetes Mellitus
Primates
Rodentia
Eating
Kidney
Glucose
Injections

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Hara, H., Lin, Y-J., Zhu, X., Tai, H. C., Ezzelarab, M., Balamarugan, A. N., ... Cooper, D. K. C. (2008). Safe induction of diabetes by high-dose streptozotocin in pigs. Pancreas, 36(1), 31-38. https://doi.org/10.1097/mpa.0b013e3181452886
Hara, Hidetaka ; Lin, Yih-Jyh ; Zhu, Xiaocheng ; Tai, Hao Chih ; Ezzelarab, Mohamed ; Balamarugan, A. N. ; Bottino, Rita ; Houser, Stuart L. ; Cooper, David K.C. / Safe induction of diabetes by high-dose streptozotocin in pigs. In: Pancreas. 2008 ; Vol. 36, No. 1. pp. 31-38.
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Hara, H, Lin, Y-J, Zhu, X, Tai, HC, Ezzelarab, M, Balamarugan, AN, Bottino, R, Houser, SL & Cooper, DKC 2008, 'Safe induction of diabetes by high-dose streptozotocin in pigs', Pancreas, vol. 36, no. 1, pp. 31-38. https://doi.org/10.1097/mpa.0b013e3181452886

Safe induction of diabetes by high-dose streptozotocin in pigs. / Hara, Hidetaka; Lin, Yih-Jyh; Zhu, Xiaocheng; Tai, Hao Chih; Ezzelarab, Mohamed; Balamarugan, A. N.; Bottino, Rita; Houser, Stuart L.; Cooper, David K.C.

In: Pancreas, Vol. 36, No. 1, 01.01.2008, p. 31-38.

Research output: Contribution to journalArticle

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AU - Hara, Hidetaka

AU - Lin, Yih-Jyh

AU - Zhu, Xiaocheng

AU - Tai, Hao Chih

AU - Ezzelarab, Mohamed

AU - Balamarugan, A. N.

AU - Bottino, Rita

AU - Houser, Stuart L.

AU - Cooper, David K.C.

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N2 - OBJECTIVES: 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. METHODS: 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. RESULTS: One to 4 weeks after STZ administration, in group 1 (150 mg/kg) pigs, insulin and C-peptide levels were detected up to 7 μIU/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 μIU/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. CONCLUSIONS: High-dose (200 mg/kg) Zanosar STZ induces diabetes safely and completely in pigs without side effects. Pancreatectomy can, therefore, be avoided.

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Hara H, Lin Y-J, Zhu X, Tai HC, Ezzelarab M, Balamarugan AN et al. Safe induction of diabetes by high-dose streptozotocin in pigs. Pancreas. 2008 Jan 1;36(1):31-38. https://doi.org/10.1097/mpa.0b013e3181452886