Development of stable STZ-induced diabetes requires coexisting diet-induced impaired glucose tolerance. Development of stable STZ-induced diabetes requires.

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Development of stable STZ-induced diabetes requires coexisting diet-induced impaired glucose tolerance. Development of stable STZ-induced diabetes requires coexisting diet-induced impaired glucose tolerance. (A) Diagrammatic representation of optimized STZ treatment to induce hyperglycemia in guinea pigs fed either normal or HFHC diet. STZ powder is dissolved in citrate buffer at 100 mg/ml, then incubated for 2 h to allow for α/β anomer equilibration. Twenty minutes before STZ treatment, guinea pigs are administered a 0.5 mg/kg dose of the α2 agonist yohimbine, by the intramuscular (IM) route. Guinea pigs are then given a single 200 mg/kg subcutaneous (SC) injection of anomer-equilibrated STZ. Diabetic hyperglycemia is determined by an oral glucose tolerance test (OGTT) at day 7, 14 and 21, based on a 2 h blood glucose ≥200 mg/dl. (B) Blood glucose concentrations were measured daily at random in nonfasted, STZ-treated guinea pigs fed a normal diet (n=5). Hyperglycemia, observable 24 h after STZ treatment, has a trend of steady decline over the course of 14 days. *P<0.05 compared with day 1 post-STZ, one-way ANOVA. (C) Glucose tolerance was evaluated in STZ-treated guinea pigs (n=5) fed a normal diet by standardized oral glucose challenge on day 7, 14 and 21 after STZ treatment, and compared with normal-diet controls (n=5). Fasting hyperglycemia and diabetic glucose intolerance is evident 7 days after STZ treatment, but glucose intolerance diminishes over time, returning to nondiabetic tolerance after 21 days. **P<0.01, ***P<0.001, compared with mean glucose of normal-diet controls at 0, 60 and 120 min, or day 21 challenge of STZ guinea pigs at 150 min, two-way ANOVA. (D) HFHC-fed guinea pigs were treated with STZ after 8 weeks of consuming HFHC diet. Response to an oral glucose challenge is documented over 7, 14 and 21 days after STZ treatment that was preceded by 8 weeks of HFHC feeding (n=5 or 10). STZ treatment results in stable fasting hyperglycemia and diabetic glucose intolerance persisting to 21 days after treatment when guinea pigs are challenged in the presence of HFHC diet-induced impaired glucose tolerance. *P<0.05, ***P<0.001, compared with mean glucose of normal-diet controls at that measurement time point, one-way ANOVA based on mean area under the curve. Brendan K. Podell et al. Dis. Model. Mech. 2017;10:151-162 © 2017. Published by The Company of Biologists Ltd