title: Jejunal nutrient sensing is required for duodenal-jejunal bypass surgery to rapidly lower glucose concentrations in uncontrolled diabetes.
abstract: 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.
authors.affiliation: Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Danna M
authors.initials: DM
authors.lastname: Breen
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Rasmussen
authors.forename: Andrea
authors.initials: A
authors.lastname: Kokorovic
authors.forename: Rennian
authors.initials: R
authors.lastname: Wang
authors.forename: Grace W C
authors.initials: GW
authors.lastname: Cheung
authors.forename: Tony K T
authors.initials: TK
authors.lastname: Lam
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D004386:Duodenum / Q000601:surgery*; D015390:Gastric Bypass; D007583:Jejunum / Q000601:surgery*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D013311:Streptozocin