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

Patel, Rajesh; Shukla, Alpana; Ahn, Soo Min; Moreira, Marlus; Rubino, Francesco

doi:10.1002/oby.20441

Cited by 44 publications

(28 citation statements)

References 44 publications

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“…The GIP response to the oral glucose load was similarly unaffected by these procedures, suggesting that, at least in these animals, the effect of these operations is not mediated by changes in these incretins. These results are consistent with those of at least two recent studies (10,38) showing that GLP-1 levels are not dramatically elevated shortly after DJB. This is in contrast with the evidence that RYGB and sleeve gastrectomy result in rapid and large elevations of GLP-1 in response to oral glucose or mixed-meal tests both in humans and rodents.…”

Section: Discussionsupporting

confidence: 93%

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Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats Without Changes in Incretins or Insulin Secretion

et al. 2014

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Gastric bypass surgery can dramatically improve type 2 diabetes. It has been hypothesized that by excluding duodenum and jejunum from nutrient transit, this procedure may reduce putative signals from the proximal intestine that negatively influence insulin sensitivity (SI). To test this hypothesis, resection or bypass of different intestinal segments were performed in diabetic Goto-Kakizaki and Wistar rats. Rats were randomly assigned to five groups: duodenal-jejunal bypass (DJB), jejunal resection (jejunectomy), ileal resection (ileectomy), pair-fed sham-operated, and nonoperated controls. Oral glucose tolerance test was performed within 2 weeks after surgery. Baseline and poststimulation levels of glucose, insulin, glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured. Minimal model analysis was used to assess SI. SI improved after DJB (SI = 1.14 ± 0.32 × 10(-4) min(-1) ⋅ pM(-1)) and jejunectomy (SI = 0.80 ± 0.14 × 10(-4) min(-1) ⋅ pM(-1)), but not after ileectomy or sham operation/pair feeding in diabetic rats. Both DJB and jejunal resection normalized SI in diabetic rats as shown by SI levels equivalent to those of Wistar rats (SI = 1.01 ± 0.06 × 10(-4) min(-1) ⋅ pM(-1); P = NS). Glucose effectiveness did not change after operations in any group. While ileectomy increased plasma GIP levels, no changes in GIP or GLP-1 were observed after DJB and jejunectomy. These findings support the hypothesis that anatomic alterations of the proximal small bowel may reduce factors associated with negative influence on SI, therefore contributing to the control of diabetes after gastric bypass surgery

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Section: Discussionsupporting

confidence: 93%

“…The discrepancy might be due to the fact that RYGB and sleeve gastrectomy, unlike DJB, involve significant manipulations of gastric anatomy. In fact, a recent study (38) suggests that changes in GLP-1 response to nutrient stimuli may result from alterations of gastric physiology rather than from intestinal rerouting as previously believed.…”

Section: Discussionmentioning

confidence: 92%

Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats Without Changes in Incretins or Insulin Secretion

et al. 2014

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“…In the study by Hu et al 11 , DJB was also unable to reduce the body weight of animals previously fed with a highcalorie diet and a standard diet for 12 weeks after surgery. According to Patel et al 21 , rats submitted to DJB showed no changes in the concentration of fasting ghrelin, a hormone involved in regulating food intake. Thus, it is suggested that animals did not lose weight after DJB because this surgical procedure does not provoke a change in food intake.…”

Section: ■ Discussionmentioning

confidence: 99%

Effects of duodenal-jejunal bypass on structure of diaphragm in western diet obese rats

et al. 2017

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Effects of duodenal-jejunal bypass on structure of diaphragm in western diet obese rats 1 1-Experimental SurgeryActa Cir Bras. 2017;32(1):1-13 Abstract Purpose: To evaluate the effects of duodenal-jejunal bypass (DJB) on the diaphragm muscle of obese rats fed on a western diet (WD). Methods: Eighteen male Wistar rats were fed a standard rodent chow diet (CTL group) or WD ad libitum. After 10 weeks, WD rats were submitted to sham (WD SHAM) or duodenal-jejunal bypass (WD DJB). The structure, ultrastructure, collagen content and the morphometry of the neuromuscular junctions (NMJs) were analyzed two months after surgery. Results: WD SHAM rats displayed an increase in body weight, the Lee index and retroperitoneal and peri-epididymal fat pads compared to the CTL group. DJB did not alter these parameters. The muscle fiber structure and NMJs were similar in the WD SHAM and CTL groups. However, the WD SHAM group showed alterations in the fiber ultrastructure, such as loosely arranged myofibrils and Z line disorganization. In addition, WD SHAM animals presented a considerable amount of lipid droplets and a reduction in the percentage of collagen compared to the CTL group. DJB did not affect the structure or ultrastructure of the muscle fibers or the NMJs in the diaphragm of the WD DJB animals. Conclusion: Duodenal-jejunal bypass did not improve the alterations observed in the diaphragm of western diet obese-rats.

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“…Also, recent studies using mice models of functional GLP-1 deficiency, GLP-1 receptor knockout mice (20), and inhibition of GLP-1 receptor by exendin(9-39) in humans (21) call into question the role of GLP-1, suggesting that the mechanisms of action of RYGB are more complex. RYGB excludes the duodenum and jejunum from the transit of nutrients, which seems to have specific antidiabetes effects (22,23). Given the close anatomic relationship between the duodenum and the pancreas, one cannot exclude that changes in regional/paracrine neuroendocrine mechanisms could also influence b-cell function and growth.…”

mentioning

confidence: 99%

“…RYGB excludes the duodenum and jejunum from the transit of nutrients, which seems to have specific antidiabetes effects (22,23). Given the close anatomic relationship between the duodenum and the pancreas, one cannot exclude that changes in regional/paracrine neuroendocrine mechanisms could also influence b-cell function and growth.…”

mentioning

confidence: 99%

Is the Gut the “Sweet Spot” for the Treatment of Diabetes?

Rubino

Amiel

2014

Diabetes

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Oskar Minkowski possessed a rare combination of talents: He was an internist with the intuition of a scientist and the dexterity of a surgeon. One day in 1889, he and his colleague Joseph von Mering at the University of Strasbourg performed a total pancreatectomy in a dog to investigate if pancreatic enzymes were necessary to break down fatty acids in the gut. The dog survived the operation but unexpectedly developed polyuria, thirst, hunger, and glycosuria. Minkowski joined the dots to realize the link between the pancreas and diabetes (1).This story is just one example of how surgical manipulations of anatomy can play a major role in advancing knowledge about physiology and disease. Many lessons about the functioning of the central nervous system, the pituitary gland, and the adrenals have been learned through the help of a scalpel (2), and Minkowski's observation provided the fundamental clue that lead to the discovery of insulin by Banting and Best in 1921. More than a century later, surgery may again provide a unique opportunity to improve our understanding of glucose homeostasis, diabetes, and b-cell growth. Readers of Diabetes will know that a number of gastrointestinal (GI) operations used to cause weight loss (bariatric surgery) has also been shown to cause remission of type 2 diabetes (T2D) (3,4) as well as improvement of hypertension and dyslipidemia (5) and reduction of cardiovascular disease and death associated with diabetes and obesity (6). The mechanisms by which these operations control diabetes have become the subject of intense research in recent years, fueled by the experimental evidence that GI bypass surgeries can induce very rapid antidiabetes effects, independent of weight loss (7).The pathophysiology of T2D is complex but the disease is characterized by a combination of insulin resistance and defective insulin secretion that worsens over time (8); treatments of curative intent would need to address both defects. GI bypass procedures can improve insulin sensitivity and production (9,10), suggesting that the GI tract may be a "sweet spot" for diabetes treatment.In particular, Roux-en-Y gastric bypass (RYGB) restores first-phase insulin response (10) and results in hypersecretion of C-peptide and insulin following nutrient ingestion (11), suggesting enhancement of b-cell function (12). Increased b-cell mass has also been hypothesized following controversial reports of nesidioblastosis complicating RYGB (13). Other hints of an effect of GI surgery on b-cell growth derive from observations of increased PDX1 levels (14) and prevention of b-cell loss after experimental duodenal-jejunal bypass in rodents (15), as well as from case reports of heterotopic pancreatic mass after RYGB in humans (16).Lindqvist et al. (17) add support to the hypothesis that RYGB can stimulate b-cell growth. In their study, morphometric analysis revealed a doubling of b-cell mass and islet number in four RYGB-treated pigs, studied 20 days after surgery and compared with pair-fed, sham-operated controls. Extraislet b-c...

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

Cited by 44 publications

References 44 publications

Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats Without Changes in Incretins or Insulin Secretion

Duodenal-Jejunal Bypass and Jejunectomy Improve Insulin Sensitivity in Goto-Kakizaki Diabetic Rats Without Changes in Incretins or Insulin Secretion

Effects of duodenal-jejunal bypass on structure of diaphragm in western diet obese rats

Is the Gut the “Sweet Spot” for the Treatment of Diabetes?

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