Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

Albers, Peter H.; Bojsen‐Møller, Kirstine N.; Dirksen, Carsten; Serup, Annette Karen; Kristensen, Dorte E.; Frystyk, Jan; Clausen, T.; Kiens, Bente; Madsbad, Sten

doi:10.1152/ajpregu.00228.2014

Cited by 43 publications

(47 citation statements)

References 62 publications

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“…As Akt activates ribosomal protein S6 kinase, translation may also be playing a role in increased ribosome abundance postsurgery (25). However, a study by Albers et al (16), showed no increase in Akt activity in normoglycemic individuals at 3 months postsurgery. Additional studies would be necessary to explore the factors that regulate the gene expression of ribosomal proteins.…”

Section: Discussionmentioning

confidence: 94%

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Identification of Novel Changes in Human Skeletal Muscle Proteome After Roux-en-Y Gastric Bypass Surgery

et al. 2016

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The mechanisms of metabolic improvements after Roux-en-Y gastric bypass (RYGB) surgery are not entirely clear. Therefore, the aim of our study was to investigate the role of obesity and RYGB on the human skeletal muscle proteome. Basal muscle biopsies were obtained from seven obese (BMI >40 kg/m2) female subjects (45.1 ± 3.6 years) pre- and 3 months post-RYGB, and euglycemic-hyperinsulinemic clamps were used to assess insulin sensitivity. Four age-matched (48.5 ± 4.7 years) lean (BMI <25 kg/m2) females served as control subjects. We performed quantitative mass spectrometry and microarray analyses on protein and RNA isolated from the muscle biopsies. Significant improvements in fasting plasma glucose (104.2 ± 7.8 vs. 86.7 ± 3.1 mg/dL) and BMI (42.1 ± 2.2 vs. 35.3 ± 1.8 kg/m2) were demonstrated in the pre- versus post-RYGB, both P < 0.05. Proteomic analysis identified 2,877 quantifiable proteins. Of these, 395 proteins were significantly altered in obesity before surgery, and 280 proteins differed significantly post-RYGB. Post-RYGB, 49 proteins were returned to normal levels after surgery. KEGG pathway analysis revealed a decreased abundance in ribosomal and oxidative phosphorylation proteins in obesity, and a normalization of ribosomal proteins post-RYGB. The transcriptomic data confirmed the normalization of the ribosomal proteins. Our results provide evidence that obesity and RYGB have a dynamic effect on the skeletal muscle proteome.

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Section: Discussionmentioning

confidence: 94%

“…In our study, the BMI post-RYGB surgery was on average 35 kg/m 2 , which still is considered obese. Other studies have shown that improvements in glucose disposal occur 6–12 months postsurgery (16,17). Therefore, the lack of improvement in peripheral insulin sensitivity may be more pronounced when weight loss is more extensive.…”

Section: Discussionmentioning

confidence: 97%

Identification of Novel Changes in Human Skeletal Muscle Proteome After Roux-en-Y Gastric Bypass Surgery

et al. 2016

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“…In contrast to early hepatic effects, in both humans and rodents, it is very clear that improvements in peripheral insulin sensitivity and glucose disposal as assessed by hyperinsulinemic euglycemic clamps do not occur until after significant weight loss. In fact, long‐term weight loss–adjusted results suggest that weight loss–independent metabolic effects are important early after surgery but that the sustained weight loss is more of a factor for the long‐term reductions in basal glucose and insulin and consequent reductions in HOMA‐IR .…”

Section: Bariatric Surgery Glucose Homeostasis and T2dm Resolutionmentioning

confidence: 98%

“…Early after surgery (days to ∼2 weeks) the most robust change in glucose homeostasis in patients with frank diabetes or with impaired glucose tolerance is the reduction in fasting plasma glucose and/or insulin levels and consequently homeostatic model assessment for assessing β‐cell function and insulin resistance (HOMA‐IR), an index of insulin sensitivity calculated using fasting glucose and insulin levels. Some of this rapid improvement could certainly occur through removal of glucotoxicity, which affects insulin secretion and insulin‐mediated glucose disposal (i.e., the impact of chronically high glucose levels itself impairs insulin secretion and glucose disposal) .…”

Section: Bariatric Surgery Glucose Homeostasis and T2dm Resolutionmentioning

confidence: 99%

Physiological and molecular responses to bariatric surgery: markers or mechanisms underlying T2DM resolution?

Hutch

Sandoval

2016

Annals of the New York Academy of Sciences

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Bariatric surgery is currently the most effective treatment for obesity and associated comorbidities, including rapid resolution of type 2 diabetes mellitus (T2DM). Although the weight loss itself has substantial impact, bariatric surgery also has weight loss-independent effects on T2DM. Several variations of bariatric surgery exist, including the widely studied Roux-en-Y gastric bypass and vertical sleeve gastrectomy. The success of both of these bariatric surgeries was originally attributed to restrictive and malabsorptive modes of action; however, mounting evidence from both human and animal studies implicates mechanisms beyond surgery-induced mechanical changes to the gastrointestinal (GI) system. In fact, with bariatric surgery comes a spectrum of physiological responses, including postprandial enhancement of gut peptide and bile acids levels, restructuring of microbial composition, and changes in GI function and morphology. Although many of these processes are also essential for glucoregulation, the independent role of each in the success of surgery is still an open question. In this review, we explore whether these changes are necessary for the improvements in body mass and glucose homeostasis or whether they are simply markers of the physiological effect of surgery.

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“…Early after RYGB surgery, an enhanced insulin secretion rate and enhanced circulating GLP-1 levels have been documented (10,11). However, it takes months before peripheral insulin sensitivity is detected (9,12), which parallels enhanced muscle expression of GLUT4, enhanced mitochondrial respiration, and enhanced phosphorylation of Akt and TBC1D4 (13)(14)(15). Transcriptomic profiling performed in skeletal muscle before and 6 months after RYGB has documented a partial normalization of alterations detected in obesity, namely, affecting gene pathways related to lipid metabolism or mitochondria (16).…”

mentioning

confidence: 99%

The Muscle Race After Bariatric Surgery: Ribosomal Proteins Come First

Hernández‐Álvarez

Zorzano

2016

Diabetes

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Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

Abstract: . Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery.

Cited by 43 publications

References 62 publications

Identification of Novel Changes in Human Skeletal Muscle Proteome After Roux-en-Y Gastric Bypass Surgery

Identification of Novel Changes in Human Skeletal Muscle Proteome After Roux-en-Y Gastric Bypass Surgery

Physiological and molecular responses to bariatric surgery: markers or mechanisms underlying T2DM resolution?

The Muscle Race After Bariatric Surgery: Ribosomal Proteins Come First

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