HFHC/STZ guinea pigs develop insulin-independent diabetes that is responsive to oral antihyperglycemic therapy. HFHC/STZ guinea pigs develop insulin-independent.

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HFHC/STZ guinea pigs develop insulin-independent diabetes that is responsive to oral antihyperglycemic therapy. HFHC/STZ guinea pigs develop insulin-independent diabetes that is responsive to oral antihyperglycemic therapy. (A) Diabetic HFHC/STZ guinea pigs received either a combination of metformin and glipizide therapy (HFHC/STZ Tx, n=4), initiated 21 days after STZ treatment, or remained with uncontrolled diabetes (HFHC/STZ UnTx, n=4). Responses to an oral glucose challenge were compared with normal-diet controls (n=2). Metformin and glipizide treatment in HFHC/STZ guinea pigs reverses diabetic glucose intolerance and fasting hyperglycemia. ***P<0.001, one-way ANOVA. (B) Survival was tracked for 120 days in HFHC/STZ guinea pigs that were either treated with metformin and glipizide or remained with uncontrolled diabetes, compared with normal-diet control guinea pigs. Antihyperglycemic therapy significantly improves survival in guinea pigs with HFHC/STZ diabetes. *P<0.05. (C) Immunofluorescent detection of pro-insulin after 120 days of treatment in HFHC/STZ guinea pigs treated with metformin and glipizide combination therapy. Reduced β-cell frequency remains present after 120 days in the presence of combination therapy. (D) Immunofluorescent detection of pro-insulin in HFHC/STZ guinea pigs with uncontrolled diabetes. Insulin production appears similar to those receiving combination therapy. (E) Immunofluorescent detection of pro-insulin in a normal-diet control guinea pig from the survival group, demonstrating a greater frequency of β cells in the absence of diabetogenic treatment. (F) Quantitation of pro-insulin-positive cells expressed as a percentage of tissue area from six representative fields per treatment group. HFHC/STZ treatment reduces total β-cell mass, which increases in guinea pigs treated with metformin and glipizide. *P<0.05, ***P<0.001, compared with untreated HFHC/STZ guinea pigs, one-way ANOVA. Scale bars: 100 μm. Brendan K. Podell et al. Dis. Model. Mech. 2017;10:151-162 © 2017. Published by The Company of Biologists Ltd