title: Duodenal-jejunal bypass protects GK rats from {beta}-cell loss and aggravation of hyperglycemia and increases enteroendocrine cells coexpressing GIP and GLP-1.
abstract: Dramatic improvement of type 2 diabetes is commonly observed after bariatric surgery. However, the mechanisms behind the alterations in glucose homeostasis are still elusive. We examined the effect of duodenal-jejunal bypass (DJB), which maintains the gastric volume intact while bypassing the entire duodenum and the proximal jejunum, on glycemic control, β-cell mass, islet morphology, and changes in enteroendocrine cell populations in nonobese diabetic Goto-Kakizaki (GK) rats and nondiabetic control Wistar rats. We performed DJB or sham surgery in GK and Wistar rats. Blood glucose levels and glucose tolerance were monitored, and the plasma insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured. β-Cell area, islet fibrosis, intestinal morphology, and the density of enteroendocrine cells expressing GLP-1 and/or GIP were quantified. Improved postprandial glycemia was observed from 3 mo after DJB in diabetic GK rats, persisting until 12 mo after surgery. Compared with the sham-GK rats, the DJB-GK rats had an increased β-cell area and a decreased islet fibrosis, increased insulin secretion with increased GLP-1 secretion in response to a mixed meal, and an increased population of cells coexpressing GIP and GLP-1 in the jejunum anastomosed to the stomach. In contrast, DJB impaired glucose tolerance in nondiabetic Wistar rats. In conclusion, although DJB worsens glucose homeostasis in normal nondiabetic Wistar rats, it can prevent long-term aggravation of glucose homeostasis in diabetic GK rats in association with changes in intestinal enteroendocrine cell populations, increased GLP-1 production, and reduced β-cell deterioration.
authors.affiliation: Dept. of Cellular and Physiological Sciences, Life Sciences Institute, Univ. of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Speck
authors.forename: Young Min
authors.initials: YM
authors.lastname: Cho
authors.forename: Ali
authors.initials: A
authors.lastname: Asadi
authors.forename: Francesco
authors.initials: F
authors.lastname: Rubino
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kieffer
mesh_terms: D000818:Animals; D050110:Bariatric Surgery; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000601:surgery*; D004386:Duodenum / Q000502:physiology*; D004703:Endocrine System / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005355:Fibrosis; D005749:Gastric Inhibitory Polypeptide / Q000096:biosynthesis*; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis*; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000097:blood*; D007150:Immunohistochemistry; D054795:Incretins / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D007515:Islets of Langerhans / Q000473:pathology; D007583:Jejunum / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D054795:Incretins; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1