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GK-rats respond to gastric bypass surgery with improved glycemia despite unaffected insulin secretion and beta cell mass

Miskelly, Michael G. LU ; Shcherbina, Liliya LU ; Thorén Fischer, Ann Helen LU ; Abels, Mia LU ; Lindqvist, Andreas LU and Wierup, Nils LU (2021) In Peptides 136.
Abstract

Roux-en-Y gastric bypass (RYGB) is the most effective treatment for morbid obesity and results in rapid remission of type 2 diabetes (T2D), before significant weight loss occurs. The underlying mechanisms for T2D remission are not fully understood. To gain insight into these mechanisms we used RYGB-operated diabetic GK-rats and Wistar control rats. Twelve adult male Wistar- and twelve adult male GK-rats were subjected to RYGB- or sham-operation. Oral glucose tolerance tests (OGTT) were performed six weeks after surgery. RYGB normalized fasting glucose levels in GK-rats, without affecting fasting insulin levels. In both rat strains, RYGB caused increased postprandial responses in glucose, GLP-1, and GIP. RYGB caused elevated postprandial... (More)

Roux-en-Y gastric bypass (RYGB) is the most effective treatment for morbid obesity and results in rapid remission of type 2 diabetes (T2D), before significant weight loss occurs. The underlying mechanisms for T2D remission are not fully understood. To gain insight into these mechanisms we used RYGB-operated diabetic GK-rats and Wistar control rats. Twelve adult male Wistar- and twelve adult male GK-rats were subjected to RYGB- or sham-operation. Oral glucose tolerance tests (OGTT) were performed six weeks after surgery. RYGB normalized fasting glucose levels in GK-rats, without affecting fasting insulin levels. In both rat strains, RYGB caused increased postprandial responses in glucose, GLP-1, and GIP. RYGB caused elevated postprandial insulin secretion in Wistar-rats, but had no effect on insulin secretion in GK-rats. In agreement with this, RYGB improved HOMA-IR in GK-rats, but had no effect on HOMA-β. RYGB-operated GK-rats had an increased number of GIP receptor and GLP-1 receptor immunoreactive islet cells, but RYGB had no major effect on beta or alpha cell mass. Furthermore, in RYGB-operated GK-rats, increased Slc5a1, Pck2 and Pfkfb1 and reduced Fasn hepatic mRNA expression was observed. In summary, our data shows that RYGB induces T2D remission and enhanced postprandial incretin hormone secretion in GK-rats, without affecting insulin secretion or beta cell mass. Thus our data question the dogmatic view of how T2D remission is achieved and instead point at improved insulin sensitivity as the main mechanism of remission.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gastric bypass, GIP, GK, GLP-1, Incretin receptor, Incretins, Insulin, Pancreas, Roux-en-Y gastric bypass, RYGB
in
Peptides
volume
136
article number
170445
publisher
Elsevier
external identifiers
  • scopus:85097245489
  • pmid:33197511
ISSN
0196-9781
DOI
10.1016/j.peptides.2020.170445
language
English
LU publication?
yes
id
0ed65a27-7c0c-41cd-87aa-7d9c0c3fee92
date added to LUP
2020-12-15 05:04:11
date last changed
2021-02-23 03:37:36
@article{0ed65a27-7c0c-41cd-87aa-7d9c0c3fee92,
  abstract     = {<p>Roux-en-Y gastric bypass (RYGB) is the most effective treatment for morbid obesity and results in rapid remission of type 2 diabetes (T2D), before significant weight loss occurs. The underlying mechanisms for T2D remission are not fully understood. To gain insight into these mechanisms we used RYGB-operated diabetic GK-rats and Wistar control rats. Twelve adult male Wistar- and twelve adult male GK-rats were subjected to RYGB- or sham-operation. Oral glucose tolerance tests (OGTT) were performed six weeks after surgery. RYGB normalized fasting glucose levels in GK-rats, without affecting fasting insulin levels. In both rat strains, RYGB caused increased postprandial responses in glucose, GLP-1, and GIP. RYGB caused elevated postprandial insulin secretion in Wistar-rats, but had no effect on insulin secretion in GK-rats. In agreement with this, RYGB improved HOMA-IR in GK-rats, but had no effect on HOMA-β. RYGB-operated GK-rats had an increased number of GIP receptor and GLP-1 receptor immunoreactive islet cells, but RYGB had no major effect on beta or alpha cell mass. Furthermore, in RYGB-operated GK-rats, increased Slc5a1, Pck2 and Pfkfb1 and reduced Fasn hepatic mRNA expression was observed. In summary, our data shows that RYGB induces T2D remission and enhanced postprandial incretin hormone secretion in GK-rats, without affecting insulin secretion or beta cell mass. Thus our data question the dogmatic view of how T2D remission is achieved and instead point at improved insulin sensitivity as the main mechanism of remission.</p>},
  author       = {Miskelly, Michael G. and Shcherbina, Liliya and Thorén Fischer, Ann Helen and Abels, Mia and Lindqvist, Andreas and Wierup, Nils},
  issn         = {0196-9781},
  language     = {eng},
  publisher    = {Elsevier},
  series       = {Peptides},
  title        = {GK-rats respond to gastric bypass surgery with improved glycemia despite unaffected insulin secretion and beta cell mass},
  url          = {http://dx.doi.org/10.1016/j.peptides.2020.170445},
  doi          = {10.1016/j.peptides.2020.170445},
  volume       = {136},
  year         = {2021},
}