Absence of intestinal gluconeogenesis in type 1 diabetic rats: Arteriovenous and carbon 13 NMR measurements.

Abstract

Recent reports have indicated that type 1 diabetes induces gluconeogenesis in the small intestine of adult Sprague Dawley rats in vivo. Since this would (i) represent a dramatic revision of the prevailing view that only the liver and the kidneys are gluconeogenic, and (ii) have major consequences in the diabetes fields, we have thoroughly re‐examined this question. For this, metabolically viable small intestinal segments from fed and 36h‐fasted streptozotocin‐diabetic Sprague Dawley rats were incubated with [3–13C]glutamine as substrate. After incubation, substrate utilization and product accumulation were measured by enzymatic and NMR methods. Although the segments utilized 13C‐glutamine and accumulated 13C‐labeled products at high rates for 30 min in vitro, no substantial glucose synthesis could be detected. This was not due to the re‐utilization of 13C‐glucose initially synthesized. Arteriovenous metabolite concentration difference measurements across the portal vein‐drained viscera of 36h‐fasted streptozotocin‐diabetic Sprague‐Dawley rats clearly indicated that glutamine, the main if not the only gluconeogenic precursor taken up, could not give rise to detectable glucose production in vivo. Therefore, we challenge the view that the small intestine of the type 1 diabetic rat is a gluconeogenic organ.Supported by the INSERM.