Mechanisms in bariatric surgery: Gut hormones, diabetes resolution, and weight loss

Holst, Jens J.; Madsbad, Sten; Bojsen‐Møller, Kirstine N.; Svane, Maria S.; Jørgensen, Nils B.; Dirksen, Carsten; Martinussen, Christoffer

doi:10.1016/j.soard.2018.03.003

Cited by 170 publications

(117 citation statements)

References 66 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…19 RYGB and VSG are characterized by accelerated transport of nutrients into the distal intestine and by rapid and robust improvement in hepatic insulin resistance and blood glucose levels postoperatively. 20 In our study, a significant decrease in FST was achieved after only 3 months, indicating a rapid change in circulating profile, whereas the changes in FSTL3 were in the same direction but more modest. The current study has some limitations.…”

Section: Insupporting

confidence: 42%

“…Generally, AGB does not affect time of gastric emptying and is associated with slower weight loss and less profound metabolic benefit compared to other bariatric interventions . RYGB and VSG are characterized by accelerated transport of nutrients into the distal intestine and by rapid and robust improvement in hepatic insulin resistance and blood glucose levels postoperatively . In our study, a significant decrease in FST was achieved after only 3 months, indicating a rapid change in circulating profile, whereas the changes in FSTL3 were in the same direction but more modest.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Follistatins in glucose regulation in healthy and obese individuals

Perakakis

Kokkinos

Peradze

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Aims It has been suggested recently that follistatin (FST) and its homologous protein, follistatin‐like 3 (FSTL3), may be a therapeutic target in the treatment of type 2 diabetes because of their glucose‐regulatory effects in rodents. Materials and Methods We investigated this hypothesis in humans by studying the physiology of a possible glycaemia–follistatin feedback loop, that is, whether glucose, but not lipid intake (oral or intravenous), can regulate circulating FST and FSTL3 in healthy humans (n = 32), whether the levels of follistatins change in response to various types of bariatric operation in morbidly obese individuals, with or without type 2 diabetes (n = 41), and whether such changes are associated prospectively with improvement of glucose homeostasis/insulin sensitivity. Results In healthy individuals, circulating FST decreases after intravenous or oral glucose intake compared to controls, indicating the presence of a negative feedback mechanism. In morbid obesity, insulin resistance, glycaemia, circulating FST and FSTL3 are all reduced (by 22%‐33%) after Roux‐en‐Y gastric bypass (RYGB) and sleeve gastrectomy. Importantly, the changes in circulating FST 3 months after bariatric surgery are associated prospectively with the changes in glucose, insulin, HOMA‐IR and HbA1c observed 6 months postoperatively in individuals with and without type 2 diabetes. Conclusions Our findings provide evidence of an important role of FST in glucose homeostasis in healthy individuals as well as in severely obese individuals with insulin resistance and type 2 diabetes. Our data extend recent results from animal studies to humans and support the need for further evaluation of FST inactivation strategies for targeting hyperglycaemia and insulin resistance.

show abstract

Section: Insupporting

confidence: 42%

Section: Discussionmentioning

confidence: 99%

Follistatins in glucose regulation in healthy and obese individuals

Perakakis

Kokkinos

Peradze

et al. 2018

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…They have also been observed to improve cardiovascular health, increase glucagon secretion and glycosuria [27][28][29] . Interestingly, bariatric surgery has also been shown to improve T2D, cardiovascular health and increase glucagon [30][31][32] . It was previously reported by one of us 33 that SGLT2 expression is down regulated in the kidney cortex following duodenal jejunal bypass in lean rats.…”

mentioning

confidence: 99%

Vertical sleeve gastrectomy lowers kidney SGLT2 expression in the mouse

Akalestou

López-Noriega

Leclerc

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Bariatric surgery has been established to improve insulin sensitivity and glucose clearance, but also increases insulin and glucagon secretion. Each of the above effects have also been observed following treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors. Aim: To determine whether there is an effect of bariatric surgery (Vertical Sleeve Gastrectomy; VSG) on renal SGLT2 expression in mice. Methods: Eighteen lean mice underwent VSG (n=8) or sham (n=9) surgery. Glucose tolerance tests with or without treatment with the SGLT2 inhibitor dapagliflozin were performed four weeks post operatively, in order to assess if pharmacological SGLT2 inhibition has the same euglycemic effects after bariatric surgery. Kidneys were harvested from fed mice and SGLT2 expression was analysed using Quantitative reverse-transcription PCR and immunofluorescence.Results: VSG mice displayed significantly improved glucose tolerance (AUC=103±6.8; AUC=66.6±2.9 in control and VSG mice, respectively; p<0.001), despite an absence of significant weight loss when compared to sham operated mice (p=0.37, Mann-Whitney test). Treatment of sham-operated mice with dapagliflozin (10 mg/kg) improved glucose tolerance. In contrast, dapagliflozin did not further improve glucose tolerance in VSG-operated mice. Moreover, qRT-PCR and immunofluorescence analysis on mouse kidneys demonstrated a significant lowering of SGLT2 expression at both the mRNA (n=7, p<0.0001) and protein (n=5, p=0.0007) levels four weeks after VSG. Conclusions: Vertical sleeve gastrectomy in lean animals causes a significant inhibition of SGLT2 expression in the kidney cortex. These findings are in line with our previous results on the effects of Duodenal Jejunal Bypass in lean rats, and point towards a physiologically-relevant gut-kidney axis. SGLT2 inhibition may thus be an important mechanism through which bariatric surgery improves glucose tolerance in man.

show abstract

“…Increase in incretin concentrations caused by bariatric surgery is a major factor contributing to its optimal effects on insulin action and FIGURE 1 A schematic overview of the equilibrium between incretin and anti-incretin actions in the normal state resistance. 24 Postoperatively, the earliest optimal metabolic event is the dramatic change in hepatic IR, which reaches approximately 50% of preoperative values. At that time, IR values are equivalent to those obtained in matched, glucose-tolerant individuals.…”

Section: Changes In Incretin Physiology After Bariatric Surgery: Thmentioning

confidence: 99%

Anti‐incretin effect: The other face of Janus in human glucose homeostasis

et al. 2019

View full text Add to dashboard Cite

The provocative idea that type 2 diabetes (T2D) may be a surgically treated disorder is based on accumulating evidence suggesting impressive remission rates of obesity and diabetes following bariatric surgery interventions. According to the "anti-incretin" theory, ingestion of food in the gastrointestinal (GI) tract, apart from activating the welldescribed incretin effect, also results in the parallel stimulation of a series of negative feedback mechanisms (anti-incretin effect). The primary goal of these regulations is to counteract the effects of incretins and other postprandial glucose-lowering adaptive mechanisms. Disruption of the equilibrium between incretins and anti-incretins could be an additional pathway leading to the development of insulin resistance and hyperglycemia. This theory provides an alternative theoretical framework to explain the mechanisms behind the optimal effects of metabolic surgery on T2D and underlines the importance of the GI tract in the homeostatic regulation of energy balance in humans. The anti-incretin concept is currently based on a limited amount of evidence and certainly requires further validation by additional studies. The aim of the present review is to discuss and critically evaluate recent evidence on the anti-incretin theory, providing an insight into current state and future perspectives.

show abstract

Mechanisms in bariatric surgery: Gut hormones, diabetes resolution, and weight loss

Cited by 170 publications

References 66 publications

Follistatins in glucose regulation in healthy and obese individuals

Follistatins in glucose regulation in healthy and obese individuals

Vertical sleeve gastrectomy lowers kidney SGLT2 expression in the mouse

Anti‐incretin effect: The other face of Janus in human glucose homeostasis

Contact Info

Product

Resources

About