Regenerating 1 and 3b Gene Expression in the Pancreas of Type 2 Diabetic Goto-Kakizaki (GK) Rats

Caldérari, Sophie; Irminger, Jean-Claude; Giroix, Marie‐Hélène; Ehses, Jan A.; Gangnerau, Marie-Noëlle; Coulaud, Josiane; Rickenbach, Katharina; Guyader, Dominique; Halban, Philippe A.; Serradas, Patricia; Homo‐Delarche, Françoise

doi:10.1371/journal.pone.0090045

Cited by 20 publications

(12 citation statements)

References 49 publications

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“…IH also increased β cell mass by up-regulation of Reg and HGF to overcome reduced glucose-induced insulin secretion and insulin resistance, causing hyperinsulinemia and making patients more obese; this worsened their SAS anatomically. The feature of gene expression in IH-treated pancreatic β cells was in agreement with that found in GK rat islets which showed down-regulation of CD38 [29] as well as up-regulation of Reg family genes [73]. …”

Section: Discussionsupporting

confidence: 85%

Intermittent Hypoxia in Pancreatic beta Cells

Ota¹,

Takasawa²,

Yamauchi³

et al. 2015

Pancreat Disord Ther

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Sleep apnea syndrome (SAS) a highly prevalent disorder, and characterized by repetitive episodes of intermittent hypoxia (IH), i.e. recurrent episodes of oxygen desaturation during sleep, the development of daytime sleepiness, and deterioration in the quality of life. Multiple epidemiological studies have provided evidence implicating the presence of SAS as a risk factor for insulin resistance and type 2 diabetes and have reported that type 2 diabetes is associated with SAS independently of age, sex, and body habitus. One of the postulated mechanisms for the metabolic alterations associated with SAS is that IH leads to substantial alterations in both pancreatic β cell function and organ glucose homeostasis. On the other hand, hyperglycemia is known to increase the rate of β cell replication, which can provide an increased source of insulin to combat insulin resistance. Although accumulating evidence suggests associations between SAS and type 2 diabetes, the direct effect of IH on pancreatic β cell has been unknown. In this review, we focus on the impact of IH on pancreatic β cells, particularly β cell dysfunction and cell proliferation.

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Section: Discussionsupporting

confidence: 85%

Intermittent Hypoxia in Pancreatic beta Cells

Ota¹,

Takasawa²,

Yamauchi³

et al. 2015

Pancreat Disord Ther

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“…Chronic inflammation in GK islets has been demonstrated and considered as a pathophysiological contributor in T2D (29,39). In the current study, temporal expression of proinflammatory cytokines revealed two distinct stages: early priming and late amplification.…”

Section: Two-stage Inflammation In Gk Isletsmentioning

confidence: 99%

Temporal Transcriptomic and Proteomic Landscapes of Deteriorating Pancreatic Islets in Type 2 Diabetic Rats

Hou

Zhong

et al. 2017

Diabetes

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Progressive reduction in β-cell mass and function comprise the core of the pathogenesis mechanism of type 2 diabetes. The process of deteriorating pancreatic islets, in which a complex network of molecular events is involved, is not yet fully characterized. We used RNA sequencing and tandem mass tag-based quantitative proteomics technology to measure the temporal mRNA and protein expression changes of pancreatic islets in Goto-Kakizaki (GK) rats from 4 to 24 weeks of age. Our omics data set outlines the dynamics of the molecular network during the deterioration of GK islets as two stages: The early stage (4-6 weeks) is characterized by anaerobic glycolysis, inflammation priming, and compensation for insulin synthesis, and the late stage (8-24 weeks) is characterized by inflammation amplification and compensation failure. Further time course analysis allowed us to reveal 5,551 differentially expressed genes, a large portion of which have not been reported before. Our comprehensive and temporal transcriptome and proteome data offer a valuable resource for the diabetes research community and for quantitative biology.

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“…REG3B might influence the development of diabetes as it is expressed not only in the intestine but also in the pancreas, acting in pancreatic β‐cell proliferation and regeneration . Goto‐Kakizaki rats that spontaneously develop diabetes showed overexpression of islet Reg3b . This was explained as a response to the inflammation leading to islet injury .…”

Section: Discussionmentioning

confidence: 99%

“…(45,46) Goto-Kakizaki rats that spontaneously develop diabetes showed overexpression of islet Reg3b. (47) This was explained as a response to the inflammation leading to islet injury. (48) In addition, human betacell tissues of type 2 diabetics had increased expression of human Reg family members, presumably as a response to inflammation.…”

Section: Discussionmentioning

confidence: 99%

The Role of Intestinal C‐type Regenerating Islet Derived‐3 Lectins for Nonalcoholic Steatohepatitis

Bluemel

Martino²,

Lee

et al. 2018

Hepatology Communications

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C‐type regenerating islet derived‐3 (Reg3) lectins defend against pathogens and keep commensal bacteria at a distance. Deficiency of Reg3g and Reg3b facilitates alcohol‐induced bacterial translocation and alcoholic liver disease. Intestinal Reg3g is down‐regulated in animal models of diet‐induced obesity, but the functional consequences for nonalcoholic steatohepatitis (NASH) are unknown. The aim of this study was to investigate the role of Reg3 lectins in NASH. NASH was induced by a Western‐style fast‐food diet in mice deficient for Reg3g or Reg3b and in transgenic mice overexpressing Reg3g in intestinal epithelial cells (Reg3gTg). Glucose tolerance was assessed after 18 weeks and insulin resistance after 19 weeks of feeding. After 20 weeks, mice were assessed for features of the metabolic syndrome. Obesity was not different in genetically modified mice compared with their respective wild‐type littermates. Glucose intolerance, liver injury, hepatic inflammation, steatosis, fibrosis, and bacterial translocation to mesenteric lymph nodes and to the liver were not different in Reg3g‐deficient mice compared with wild‐type littermates. Plasma endotoxin levels were higher in Reg3g‐deficient mice. Reg3b deficiency protected against glucose intolerance, but liver disease, bacterial translocation, and plasma endotoxin levels were similar to wild‐type littermates. Absence of either REG3G or REG3B protein in the ileum was not compensated for by up‐regulation of the respective other REG3 protein. Transgenic Reg3g mice also developed liver injury, steatosis, and fibrosis similar to their wild‐type littermates. Conclusion: In contrast to alcoholic liver disease, loss of intestinal Reg3 lectins is not sufficient to aggravate diet‐induced obesity and NASH. This supports a multi‐hit pathogenesis in NASH. Only glucose metabolism is affected by Reg3b deficiency. (Hepatology Communications 2018;2:393‐406)

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Regenerating 1 and 3b Gene Expression in the Pancreas of Type 2 Diabetic Goto-Kakizaki (GK) Rats

Cited by 20 publications

References 49 publications

Intermittent Hypoxia in Pancreatic beta Cells

Intermittent Hypoxia in Pancreatic beta Cells

Temporal Transcriptomic and Proteomic Landscapes of Deteriorating Pancreatic Islets in Type 2 Diabetic Rats

The Role of Intestinal C‐type Regenerating Islet Derived‐3 Lectins for Nonalcoholic Steatohepatitis

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