Hexosamine pathway but not interstitial changes mediates glucotoxicity in pancreatic β-cells as assessed by cytosolic Ca2+ response to glucose

  title={Hexosamine pathway but not interstitial changes mediates glucotoxicity in pancreatic $\beta$-cells as assessed by cytosolic Ca2+ response to glucose},
  author={Kazuhiro Yanagida and Yuko Maejima and Putra Santoso and Zesemdorj Otgon-Uul and Yifei Yang and Kazuya Sakuma and Kenju Shimomura and Toshihiko Yada},
  journal={Aging (Albany NY)},
  pages={207 - 214}
Hyperglycemia impairs insulin secretion as well as insulin action, being recognized as the glucotoxicity that accelerates diabetes. [...] Key Method In this study, to explore direct effects of these alterations on β-cells, single β-cells isolated from rat islets were cultured for 3 days with high (22.3 mM) glucose (HG), compared with control 5.6 mM glucose, followed by their functional assessment by measuring cytosolic Ca2+ concentration ([Ca2+]i). The [Ca2+]i response to a physiological rise in glucose…Expand
The impairment of glucose-stimulated insulin secretion in pancreatic β-cells caused by prolonged glucotoxicity and lipotoxicity is associated with elevated adaptive antioxidant response.
  • Jingqi Fu, Qi Cui, +6 authors J. Pi
  • Biology, Medicine
  • Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2017
Systems to study how chronic glucotoxicity and lipotoxicity might be linked to the impairment of glucose-stimulated insulin secretion (GSIS) machinery in pancreatic β-cells concluded that persistent glucot toxicity- and/or lipotoxic-mediated oxidative stress and subsequent adaptive antioxidant response impair glucose-derived ROS signaling and GSIS in pancreato-cells. Expand
Subchronic toxicity evaluation of glucosamine and glucosamine in combination with chondroitin sulfate in obese Zucker rats.
The studies suggest that the risk of adverse effects of oral D-glucosamine is small compared to that of hyperglycemia in these animals, but the potential for TGFβ1-mediated pathologies, such as osseous metaplasia and renal nephropathy may be increased. Expand
Phosphatase and Tensin Homologue (PTEN)-Induced Putative Kinase 1 Promotes Pancreatic Β-Cells Proliferation in Glucotoxicity Through Activation of Akt/Mtor/Hif-1α Pathway
Sustained high glucose is harmful to pancreatic β-cells, resulting in impaired pancreatic β-cells proliferation. Understanding the molecular mechanisms related to β-cells proliferation is pivotal forExpand
Redox imbalance stress in diabetes mellitus: Role of the polyol pathway
  • Liang-Jun Yan
  • Chemistry, Medicine
  • Animal models and experimental medicine
  • 2018
A potential intervention using nicotinamide riboside to restore redox balance as an approach to fighting diabetes is discussed, and the roles of this pathway in NADH/NAD+ redox imbalance stress and oxidative stress in diabetes are highlighted. Expand
Prenatal Hyperglycemia Exposure and Cellular Stress, a Sugar-Coated View of Early Programming of Metabolic Diseases
This work decided to further explore the relationship between early glucose exposure and cellular stress in the context of early development, and focus on the concept of glycemic memory, its consequences, and sexual dimorphic and epigenetic aspects. Expand
Expression and localization of the AT1 and AT2 angiotensin II receptors and α1A and α1D adrenergic receptors in aorta of hypertensive and diabetic rats
Investigation of the possible changes in the expression or localization of α1-AR (α1A and α1D) and angiotensin II receptors in aorta of rats after 4 weeks of the onset of diabetes showed that diabetes and hypertension modify the expression of the receptors in tunica intima and tunica media of aortA in a different way. Expand
Chronic mTOR Inhibition by Rapamycin and Diabetes
It is proposed that mitochondrial complex I, an enzyme responsible for NAD+ regeneration from NADH, plays an important role in rapamycin diabetes and Studying complex I dysfunction downstream of the mTOR signaling pathway using the rap amycin diabetes platform not only will provide insights into the redox mechanisms of Rapamycin diabetogenesis, but may also help devise novel strategies to reduceRapamycin toxicity during therapy. Expand
Bloqueo de los receptores de mineralocorticoides y estimulación del sistema incretina en el tratamiento de la miocardiopatía diabética experimental
En esta Tesis se ha estudiando el posible efecto de dos tratamientos sobre el miocardio de rata diabetica, y el dano miocardico puede tener graves consecuencias para el paciente diabetico. Expand


Glucosamine-induced &bgr;-cell Dysfunction: A Possible Involvement of Glucokinase or Glucose-transporter Type 2
The data imply that glucosamine impairs glucose-induced insulin release probably through the inhibition of glucose metabolism. Expand
Role of Cytosolic Ca2+ in Impaired Sensitivity to Glucose of Rat Pancreatic Islets Exposed to High Glucose In Vitro
Observations confirm that exposure of pancreatic β-cells to high glucose concentrations induces a selective reduction of the GSIR and shows that this impaired response is reversibly restored by an additional culture with normal glucose, and suggest that the inability of glucose to provoke a [Ca2+]i rise, which is observed in the β- cells exposed tohigh glucose, may be responsible for the selective impairment of theGSIR. Expand
Activation of the Hexosamine Pathway by Glucosamine in Vivo Induces Insulin Resistance in Multiple Insulin Sensitive Tissues.
We determined the effect of infusion of glucosamine (GlcN), which bypasses the rate limiting reaction in the hexosamine pathway, on insulin-stimulated rates of glucose uptake and glycogen synthesisExpand
The molecular mechanisms of pancreatic β-cell glucotoxicity: Recent findings and future research directions
Deciphering these molecular mechanisms of β- cell glucotoxicity is a mandatory first step toward the development of therapeutic strategies to protect β-cells and improve the functional β-cell mass in type 2 diabetes. Expand
Hexosamines as mediators of nutrient sensing and regulation in diabetes.
  • D. McClain
  • Biology, Medicine
  • Journal of diabetes and its complications
  • 2002
Excess hexosamine flux leads to a coordinated response whereby fuel is shunted toward long-term storage, mirroring the "thrifty phenotype" and suggesting a mechanism by which chronic overnutrition leads to the phenotype of Type 2 diabetes. Expand
Coupling of β-Cell Desensitization by Hyperglycemia to Excessive Stimulation and Circulating Insulin in Glucose-Infused Rats
It is concluded that excessiveβ-cell stimulation rather than glucotoxicity underlies hyperglycemia-induced β-cell insensitivity and effects of hyperinsulinemia can form part of the mechanisms whereby excessive stimulation affects β- cell secretion. Expand
Single pancreatic beta-cells from normal rats exhibit an initial decrease and subsequent increase in cytosolic free Ca2+ in response to glucose.
The results demonstrate that the glucose-induced bimodal change in [Ca2+]i is a physiological response of islet beta-cells, and that the decrease and increase in [ Ca2+)i are generated by mutually-independent mechanisms which are operated through glucose metabolism by islet Beta-cells. Expand
Increased hexosamine biosynthetic pathway flux dedifferentiates INS-1E cells and murine islets by an extracellular signal-regulated kinase (ERK)1/2-mediated signal transmission pathway
Glucotoxic ER stress dedifferentiates beta cells, in the absence of apoptosis, through a transcriptional response, and these effects are mediated by the activation of ERK1/2. Expand
The hexosamine biosynthesis pathway regulates insulin secretion via protein glycosylation in mouse islets.
It is shown that inhibition of the hexosamine biosynthesis pathway decreases insulin secretion from mouse islets in response to a number of secretagogues, including glucose, which may have implications for the development of type 2 diabetes. Expand
Hexosamines, insulin resistance, and the complications of diabetes: current status.
  • M. Buse
  • Biology, Medicine
  • American journal of physiology. Endocrinology and metabolism
  • 2006
Increased flux through HBP is required and sufficient for some of the metabolic effects of sustained, increased glucose flux, which promotes the complications of diabetes, e.g., diminished expression of sarcoplasmic reticulum Ca(2+)-ATPase in cardiomyocytes and induction of TGF-beta and plasminogen activator inhibitor-1 in vascular smooth muscle cells, mesangial cells, and aortic endothelial cells. Expand