C-Peptide and its Intracellular Signaling

Hills, Claire E.; Brunskill, Nigel J.

doi:10.1900/rds.2009.6.138

Cited by 19 publications

(17 citation statements)

References 59 publications

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“…However, the identification of a receptor for C-peptide has not been described previously on these cells. Evidence from multiple cell lines suggests that C-peptide-mediated effects result from stimulation of a pertussis toxin-sensitive GPCR (1,21). Recently, it was demonstrated that C-peptide stimulates cFos expression in the human erythroleukemia cell line, TF-1, and the human gastric tumor cell line, KATOIII.…”

Section: Discussionmentioning

confidence: 99%

“…The two peptides are released at equimolar concentrations, but due to differing clearance rates, circulating C-peptide levels exceed those of insulin (46). Although initially thought to be inert, recent studies have shown that C-peptide has biological activity (21,22) and has been suggested to attenuate and perhaps reverse some diabetes-associated microvascular complications (22).…”

mentioning

confidence: 99%

“…In addition, when coincubated with insulin at physiological ratios and concentrations, C-peptide has been shown to oppose the adverse effects of insulin on low O 2 -induced ATP release from healthy human erythrocytes (34). Although the signaling pathway(s) initiated by C-peptide are not well characterized, there is strong evidence that C-peptide stimulates a pertussis toxinsensitive G-protein-coupled receptor (GPCR) (21). Recently, GPR146, an orphan GPCR, was suggested to be a C-peptide receptor on KATOIII cells, based on the loss of C-peptidestimulated cFos expression after small interfering RNA (siRNA) knockdown of GPR146 (50).…”

mentioning

confidence: 99%

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Low O₂-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin

Richards

Yosten

Kolar

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Low O₂-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin

Richards

Yosten

Kolar

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…For example, Cpeptide was reported to stimulate Na + -K + -ATPase activity both in vitro and in vivo, elicit release of nitric oxide from endothelial cells, and mimic the effects of insulin in some tissues [125]. However, it is not clear whether C-peptide has any effect on liver function [126].…”

Section: C-peptidementioning

confidence: 99%

Hepatic Steatosis in Type 1 Diabetes

Regnell

Lernmark

2011

Rev Diabet Stud

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■ AbstractIslet autoimmunity in type 1 diabetes results in the loss of the pancreatic β-cells. The consequences of insulin deficiency in the portal vein for liver fat are poorly understood. Under normal conditions, the portal vein provides 75% of the liver blood supply. Recent studies suggest that non-alcoholic fatty liver disease (NAFLD) may be more common in type 1 diabetes than previously thought, and may serve as an independent risk marker for some chronic diabetic complications. The pathogenesis of NAFLD remains obscure, but it has been hypothesized that hepatic fat accumulation in type 1 diabetes may be due to lipoprotein abnormalities, hyperglycemia-induced activation of the transcription factors carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein 1c (SREBP-1c), upregulation of glucose transporter 2 (GLUT2) with subsequent intrahepatic fat synthesis, or a combination of these mechanisms. Novel approaches to non-invasive determinations of liver fat may clarify the consequences for liver metabolism when the pancreas has ceased producing insulin. This article aims to review the factors potentially contributing to hepatic steatosis in type 1 diabetes, and to assess the feasibility of using liver fat as a prognostic and/or diagnostic marker for the disease. It provides a background and a case for possible future studies in the field.

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“…These findings prompted a renewed interest in C-peptide physiology, and during the past 20 years a steadily increasing number of reports on new aspects of C-peptide physiology have emerged. The information available today includes studies of the peptide's interaction with cell membranes and its intracellular signaling properties (39,113). In vivo studies in animal models of type 1 diabetes have defined a beneficial influence of C-peptide on diabetes-induced functional and structural abnormalities of the kidney, peripheral nerves, and the central nervous system.…”

mentioning

confidence: 99%

Physiological effects and therapeutic potential of proinsulin C-peptide

Yosten

Maric‐Bilkan

Luppi

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Connecting Peptide, or C-peptide, is a product of the insulin prohormone, and is released with and in amounts equimolar to those of insulin. While it was once thought that C-peptide was biologically inert and had little biological significance beyond its role in the proper folding of insulin, it is now known that C-peptide binds specifically to the cell membranes of a variety of tissues and initiates specific intracellular signaling cascades that are pertussis toxin sensitive. Although it is now clear that C-peptide is a biologically active molecule, controversy still remains as to the physiological significance of the peptide. Interestingly, C-peptide appears to reverse the deleterious effects of high glucose in some tissues, including the kidney, the peripheral nerves, and the vasculature. C-peptide is thus a potential therapeutic agent for the treatment of diabetes-associated long-term complications. This review addresses the possible physiologically relevant roles of C-peptide in both normal and disease states and discusses the effects of the peptide on sensory nerve, renal, and vascular function. Furthermore, we highlight the intracellular effects of the peptide and present novel strategies for the determination of the C-peptide receptor(s). Finally, a hypothesis is offered concerning the relationship between C-peptide and the development of microvascular complications of diabetes.

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C-Peptide and its Intracellular Signaling

Cited by 19 publications

References 59 publications

Low O₂-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin

Low O₂-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin

Hepatic Steatosis in Type 1 Diabetes

Physiological effects and therapeutic potential of proinsulin C-peptide

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C-Peptide and its Intracellular Signaling

Cited by 19 publications

References 59 publications

Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin

Low O2-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin

Hepatic Steatosis in Type 1 Diabetes

Physiological effects and therapeutic potential of proinsulin C-peptide

Contact Info

Product

Resources

About

Low O₂-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin

Low O₂-induced ATP release from erythrocytes of humans with type 2 diabetes is restored by physiological ratios of C-peptide and insulin