Details

Autor(en) / Beteiligte

• Breen, Danna M
• Rasmussen, Brittany A
• Kokorovic, Andrea
• Wang, Rennian
• Cheung, Grace W C
• Lam, Tony K T

Titel

Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes

Ist Teil von

• Nature medicine, 2012-06, Vol.18 (6), p.950-955

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• Gastrointestinal bypass surgeries restore metabolic homeostasis in patients with type 2 diabetes and obesity(1), but the underlying mechanisms remain elusive. Duodenal-jejunal bypass surgery (DJB), an experimental surgical technique that excludes the duodenum and proximal jejunum from nutrient transit(1,2), lowers glucose concentrations in nonobese type 2 diabetic rats(2–5). Given that DJB redirects and enhances nutrient flow into the jejunum and that jejunal nutrient sensing affects feeding(6,7), the repositioned jejunum after DJB represents a junction at which nutrients could regulate glucose homeostasis. Here we found that intrajejunal nutrient administration lowered endogenous glucose production in normal rats through a gut-brain-liver network in the presence of basal plasma insulin concentrations. Inhibition of jejunal glucose uptake or formation of long chain fatty acyl-coA negated the metabolic effects of glucose or lipid, respectively, in normal rats, and altered the rapid (2 d) glucose-lowering effect induced by DJB in streptozotocin (STZ)-induced uncontrolled diabetic rats during refeeding. Lastly, in insulin-deficient autoimmune type 1 diabetic rats and STZ-induced diabetic rats, DJB lowered glucose concentrations in 2 d independently of changes in plasma insulin concentrations, food intake and body weight. These data unveil a glucoregulatory role of jejunal nutrient sensing and its relevance in the early improvement of glycemic control after DJB in rat models of uncontrolled diabetes.