scholarly journals Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats

2020 ◽  
Vol 11 ◽  
Author(s):  
Chengdong Xia ◽  
Xiuli Zhang ◽  
Tianshu Cao ◽  
Jiannong Wang ◽  
Cuidan Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Liver Injury ◽  
Er Stress ◽  
Molecular Pathogenesis ◽  
Clinical Indices ◽  
Zdf Rats ◽  
Hepatic Transcriptome

Around 9% of the adult population in the world (463 million) suffer from diabetes mellitus. Most of them (~90%) belong to type 2 diabetes mellitus (T2DM), which is a common chronic metabolic disorder, and the number of cases has been reported to increase each year. Zucker diabetic fatty (ZDF) rat provides a successful animal model to study the pathogenesis of T2DM. Although previous hepatic transcriptome studies revealed some novel genes associated with the occurrence and development of T2DM, there still lacks the comprehensive transcriptomic analysis for the liver tissues of ZDF rats. We performed comparative transcriptome analyses between the liver tissues of ZDF rats and healthy ZCL rats and also evaluated several clinical indices. We could identify 214 and 104 differentially expressed genes (DEGs) and lncRNAs in ZDF rats, respectively. Pathway and biofunction analyses showed a synergistic effect between mRNAs and lncRNAs. By comprehensively analyzing transcriptomic data and clinical indices, we detected some typical features of T2DM in ZDF rats, such as upregulated metabolism (significant increased lipid absorption/transport/utilization, gluconeogenesis, and protein hydrolysis), increased inflammation, liver injury and increased endoplasmic reticulum (ER) stress. In addition, of the 214 DEGs, 114 were known and 100 were putative T2DM-related genes, most of which have been associated with substance metabolism (particularly degradation), inflammation, liver injury and ER stress biofunctions. Our study provides an important reference and improves understanding of molecular pathogenesis of obesity-associated T2DM. Our data can also be used to identify potential diagnostic markers and therapeutic targets, which should strengthen the prevention and treatment of T2DM.

Molecular Pathogenesis of Type 2 Diabetes Mellitus and Obesity in Knockout Mice Models

2000 ◽  
Vol 28 (5) ◽  
pp. A104-A104
Author(s):  
Kazuyuki Tobe ◽  
Yasuo Terauchi ◽  
Kazuhiro Eto ◽  
Toshimasa Yamauchi ◽  
Naoto Kubota ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Knockout Mice ◽  
Molecular Pathogenesis

scholarly journals Colonic delivery of nutrients for management of blood glucose in type 2 diabetes patients

2017 ◽  
Vol 7 (1) ◽  
pp. 36
Author(s):  
Jerzy Szewczyk ◽  
JoAnn Giannone ◽  
Stefano Marcuard ◽  
Tammy Kindel ◽  
Patrick Tso ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Sustained Release ◽  
Sodium Butyrate ◽  
Colonic Delivery ◽  
L Cells ◽  
Glucose Challenge ◽  
Zdf Rats

Background: It is now widely accepted that bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) resolve or improve type 2 diabetes mellitus.  Post-prandial glucagon-like peptide-1 (GLP-1) increases after both RYGB and SG and blockade of the GLP-1 receptor suppresses the hypoglycemic effect post-operatively.  Expedited delivery of nutrients, such as L-glutamine and butyrate, to the distal small intestine and colon, where most GLP-1–secreting enteroendocrine L-cells are expressed, could explain this increase post-surgery.  Pharmacological treatments that target nutrient-sensing receptors on L-cells may mimic the effects of bariatric surgeries and may ameliorate deficiencies in gut hormone responses involved in the regulation of glucose and satiety.  In this study we investigated the effects of the colonic delivery of L-glutamine and butyrate on GLP-1 secretion and glucose homeostasis in both a pre-clinical rodent model and clinical type 2 diabetes mellitus (T2DM).  Results: Infusion of 4.4 mg of sodium butyrate, compared to saline, into the colon of Zucker diabetic fatty (ZDF) rats increased GLP-1 secretion in response to an intra-duodenal glucose challenge.  In a chronic study, oral dosing of 40 mg of sodium butyrate twice a day, formulated as colon-targeted sustained-release tablets, preserved glucose tolerance and insulin sensitivity in ZDF rats.  In ten T2DM patients requiring oral anti-hyperglymic agents, infusion of 1 g of L‑glutamine into the colon, compared to saline, increased plasma GLP-1 (p=0.017 at 30 min) and insulin (p<0.01 at 90 min; p=0.001 at 120 min; AUC p<0.005) after an oral glucose challenge.  Similar infusion with butyrate significantly increased only insulin secretion at 120 min, compared to saline (p<0.05).  Neither agent had an effect on glucose disposal.Conclusions: Targeted colonic delivery of L-glutamine and butyrate augments secretion of meal-stimulated GLP-1 and insulin.  Such an approach may be valuable for the management of hyperglycemia in T2DM patients.  A chronic clinical study with colon-targeted sustained-release L-glutamine is required to validate this hypothesis.Key words: Diabetes, nutrients, gut hormones, GLP-1, secretagogues, glucose management.

scholarly journals Peculiarities of clinical course of osteoarthritis combined with type 2 diabetes mellitus, obesity and hypertension

2018 ◽  
Vol 42 (4) ◽  
pp. 42-46
Author(s):  
Y. I. Serdulets
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Motor Function ◽  
Abdominal Obesity ◽  
Clinical Course ◽  
Pain Syndrome ◽  
Daily Activities ◽  
Clinical Indices

The aim of paper is to study the clinical indices of articular syndrome in patients with osteoarthritis combined with type 2 diabetes mellitus, obesity and hypertension. It has been found out that the combined course of osteoarthritis, abdominal obesity and type 2 diabetes mellitus is accompanied by the intensified pain syndrome in the joints, a disruption of the motor function as well as the daily activities of patients.

scholarly journals Interaction between Mitochondria and the Endoplasmic Reticulum: Implications for the Pathogenesis of Type 2 Diabetes Mellitus

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jaechan Leem ◽  
Eun Hee Koh
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Type 2 Diabetes Mellitus ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Apoptotic Cell ◽  
Peripheral Insulin Resistance ◽  
Type 2 Dm

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are closely associated withβ-cell dysfunction and peripheral insulin resistance. Thus, each of these factors contributes to the development of type 2 diabetes mellitus (DM). The accumulated evidence reveals structural and functional communications between mitochondria and the ER. It is now well established that ER stress causes apoptotic cell death by disturbing mitochondrial Ca2+homeostasis. In addition, recent studies have shown that mitochondrial dysfunction causes ER stress. In this paper, we summarize the roles that mitochondrial dysfunction and ER stress play in the pathogenesis of type 2 DM. Structural and functional communications between mitochondria and the ER are also discussed. Finally, we focus on recent findings supporting the hypothesis that mitochondrial dysfunction and the subsequent induction of ER stress play important roles in the pathogenesis of type 2 DM.

Genetics of type 2 diabetes mellitus

2011 ◽  
pp. 1734-1740 ◽  
Author(s):  
Niels Grarup ◽  
Torben Hansen ◽  
Oluf Pedersen
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Genetic Basis ◽  
Genetic Factors ◽  
Molecular Genetic ◽  
Common Type ◽  
Molecular Pathogenesis ◽  
Molecular Genetic Basis

For years, it has been well known that genetic factors are crucially important for the development of type 2 diabetes. Despite major efforts in seeking to understand the molecular genetic basis, until a few years ago, only a handful of genes responsible for relatively rare monogenic and syndromic subsets of diabetes were detected, and progress in finding genetic predispositions to common type 2 diabetes was lacking. Even though the unravelling of the molecular pathogenesis of type 2 diabetes is still in its infancy, the last few years have, nevertheless, brought some interesting developments. Box 13.3.1.1 provides a glossary of terms used currently in genetics.

scholarly journals An Exceedingly Rare Case of Liraglutide-Induced Liver Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Swetha Parvataneni ◽  
Rajarajeshwari Ramachandran ◽  
Eric Then ◽  
Tyler Grantham ◽  
Vinaya Gaduputi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Liver Injury ◽  
Complete Resolution ◽  
Receptor Agonist ◽  
Rare Case ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the treatment of type 2 diabetes mellitus. We are reporting the second case of liraglutide-induced liver injury, with complete resolution of liver injury after discontinuation of the drug.

scholarly journals Hepatic transcriptome implications for palm fruit juice deterrence of type 2 diabetes mellitus in young male Nile rats

2016 ◽  
Vol 11 (1) ◽  
Author(s):  
Soon-Sen Leow ◽  
Julia Bolsinger ◽  
Andrzej Pronczuk ◽  
K. C. Hayes ◽  
Ravigadevi Sambanthamurthi
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Fruit Juice ◽  
Young Male ◽  
Palm Fruit ◽  
Hepatic Transcriptome
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