The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats

Pacheco, David; Luis, Daniel Antonio de; Romero, Alejandro; Sagrado, M. González; Conde, Rosa; Izaola, Olatz; Aller, R.; Delgado, Alberto

doi:10.1016/j.amjsurg.2006.11.015

Cited by 107 publications

(77 citation statements)

References 22 publications

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“…19 In Goto-Kakizaki rats, a nonobese model of polygenic T2DM, this operation improved diabetesFrapidly, durably and impressivelyFeven though it caused no reduction in food intake or body weight compared with sham-operated controls. Similar observations have subsequently been made with independent investigations of non-obese diabetic Goto-Kakizaki rats 20,21 and obese diabetic Zucker rats. 18 Likewise, several small, ongoing human studies of DJB all show improvements in glycemic control, including among non-obese patients, with little or no weight loss (Cohen et al 46 and personal communications with Arguelles-Sarmiento J et al, Lakdawala M et al, and Ramos AC et al).…”

Section: The Upper Intestinal Hypothesissupporting

confidence: 85%

“…Consistent with this concept, experimental studies indicate that variations of RYGB improve T2DM not only in obese but also in nonobese diabetic animals. [18][19][20][21] Despite a growing interest in using RYGB to treat T2DM, even among less obese or non-obese patients, the underlying mechanisms of action of this procedure have not been fully evaluated. As gastrointestinal (GI) surgery appears to eliminate T2DM more effectively, rapidly and durably than any existing non-surgical method, and because the usage of bariatric surgery is rapidly increasing worldwide, elucidating the mechanisms by which these operations improve glycemia is an important research priority.…”

Section: Remission Of Diabetes After Rygbmentioning

confidence: 99%

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Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

2009

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Bariatric surgery is currently the most effective method to promote major, sustained weight loss. Roux-en-Y gastric bypass (RYGB), the most commonly performed bariatric operation, ameliorates virtually all obesity-related comorbid conditions, the most impressive being a dramatic resolution of type 2 diabetes mellitus (T2DM). After RYGB, 84% of patients with T2DM experience complete remission of this disease, and virtually all have improved glycemic control. Increasing evidence indicates that the impact of RYGB on T2DM cannot be explained by the effects of weight loss and reduced energy intake alone. Weightindependent antidiabetic actions of RYGB are apparent because of the very rapid resolution of T2DM (before weight loss occurs), the greater improvement of glucose homeostasis after RYGB than after an equivalent weight loss from other means, and the occasional development of very late-onset, pancreatic b-cell hyperfunction. Several mechanisms probably mediate the direct antidiabetic impact of RYGB, including enhanced nutrient stimulation of L-cell peptides (for example, GLP-1) from the lower intestine, intriguing but still uncharacterized phenomena related to exclusion of the upper intestine from contact with ingested nutrients, compromised ghrelin secretion, and very probably other effects that have yet to be discovered. Research designed to prioritize these mechanisms and identify potential additional mechanisms promises to help optimize surgical design and might also reveal novel pharmaceutical targets for diabetes treatment. Keywords: diabetes; gastric bypass; bariatric surgery; ghrelin; GLP-1 Bariatric operations traditionally have been thought to cause weight loss through gastric restriction and/or intestinal malabsorption. Restrictive operations such as adjustable gastric banding (AGB) create a small pouch in the proximal stomach to reduce functional gastric capacity and retard gastric emptying. Malabsorptive procedures such as biliopancreatic diversion (BPD) leave much of the stomach intact but divert ingested food from the stomach to the ileum; thus, only a small segment of the distal bowel can absorb nutrients. The typical proximal Roux-en-Y gastric bypass (RYGB) creates gastric restriction and also causes food to bypass most of the stomach and a short segment of the proximal intestine, primarily the duodenum, leaving enough intact small bowel in digestive continuity to avoid clinically significant malabsorption. RYGB causes weight loss through gastric restriction and additional mechanisms involving changes in gut hormones and other processes under active investigation. 1-14 RYGB and BPD produce the highest and most rapid rates of remission of type 2 diabetes mellitus (T2DM). Remission of diabetes after RYGBAlthough bariatric surgery was designed to facilitate weight loss, anecdotal reports of rapid postoperative remission of T2DM emerged as early as the 1970s. In 1995, Pories et al. 4 reported long term results from 608 severely obese patients who underwent gastric bypass, with a 93% follow-up rate ov...

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Section: The Upper Intestinal Hypothesissupporting

confidence: 85%

Section: Remission Of Diabetes After Rygbmentioning

confidence: 99%

Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

2009

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“…Pacheco et al (35) reported a modest decrease in postprandial plasma GLP-1 level at 1 week after DJB in GK rats, whereas Breen et al (7) reported a modest rise in GLP-1 levels in STZ-induced uncontrolled diabetic rats, and no changes in type 1 diabetic rats after DJB (7). In contrast, others (36,37) have reported modestly increased post-meal plasma GLP-1 levels after DJB, in general, however, of far less magnitude compared to the effect reported after SG and RYGB.…”

Section: Discussionmentioning

confidence: 99%

Surgical control of obesity and diabetes: The role of intestinal vs. gastric mechanisms in the regulation of body weight and glucose homeostasis

Patel

Shukla

Ahn

et al. 2013

Obesity

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Objective: To elucidate the specific role of gastric vs. intestinal manipulations in the regulation of body weight and glucose homeostasis. Design and Methods: The effects of intestinal bypass alone (duodenal-jejunal bypass -DJB) and gastric resection alone (SG) in Zucker Diabetic Fatty (ZDF) rats were compared. Additional animals underwent a combination procedure (SG þ DJB). Outcome measures included changes in weight, food intake (FI), oral glucose tolerance (GT) and gut hormones. Results: DJB did not substantially affect weight and FI, whereas SG significantly reduced weight gain and food consumption. DJB rats showed weight-independent improvement in GT, which improved less after SG. Furthermore, SG significantly suppressed plasma ghrelin and increased insulin, glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide and peptide YY response to oral glucose whereas DJB had no effects on postprandial levels of these hormones. DJB restored postprandial glucagon suppression in diabetic rats whereas SG did not affect glucagon response. The combination procedure (SG þ DJB) induced greater weight loss and better GT than SG alone without reducing food intake further. Conclusions: These findings reveal a dominant role of the stomach in the regulation of body weight and incretin response to oral glucose whereas intestinal bypass primarily affects glucose homeostasis by a weight-, insulin-and incretin-independent mechanism Obesity (2014) 21, 159-169.

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“…Nevertheless, in a cross-sectional study performed in three groups of obese women who had undergone either RYGB or LAGB or who acted as overweight controls, glucagon levels were found to be significantly reduced following a liquid meal (time point 180 min) in the RYGB group [36]. Furthermore, reduced glucagon responses to OGTTs have been observed in GK diabetic rats following DJB [37]. In line with these observations, reduced hepatic glucose production (or endogenous glucose production) has been reported in individuals treated with RYGB [38].…”

Section: Does Diabetic Hyperglucagonaemia Originate From the Proximalmentioning

confidence: 99%

Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signalling?

Knop

2009

Diabetologia

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Certain types of bariatric surgical procedures have proved not only to be effective with regard to treating obesity, but they also seem to be associated with endocrine changes which independently of weight loss give rise to remission of type 2 diabetes. Currently, it is speculated that surgical re-routing of nutrients triggers changes in the release of gastrointestine-derived hormones, which in turn cause amelioration of the diabetic state. The 'hindgut hypothesis' states that surgical re-routing of nutrients to the distal part of the small intestine results in increased secretion and concomitant glucose-lowering effects of glucagon-like peptide-1, whereas the 'foregut hypothesis' emphasises that surgical bypass of the foregut prevents the release of a hitherto unidentified nutrient-induced diabetogenic signal in susceptible individuals. Recent studies have shown that in patients with type 2 diabetes, glucagon is differentially secreted in response to oral and i.v. glucose, respectively, with lack of suppression (and initial net secretion) during oral glucose administration and a perfectly normal suppression during isoglycaemic i.v. glucose administration. These findings could point towards a role for glucagon or gut-derived glucagonotropic signalling as putative diabetogenic signals of the foregut hypothesis. In the present paper the hypotheses describing the glucoselowering mechanisms of bariatric surgical procedures sharing the common feature of a bypass of the duodenum and the proximal jejunum are outlined and a possible role for glucagon in these is proposed.

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The effects of duodenal-jejunal exclusion on hormonal regulation of glucose metabolism in Goto-Kakizaki rats

Cited by 107 publications

References 22 publications

Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery

Surgical control of obesity and diabetes: The role of intestinal vs. gastric mechanisms in the regulation of body weight and glucose homeostasis

Resolution of type 2 diabetes following gastric bypass surgery: involvement of gut-derived glucagon and glucagonotropic signalling?

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