C-peptide stimulates rat renal tubular Na+, K+-ATPase activity in synergism with neuropeptide Y

Ohtomo, Yoshiyuki; Aperia, Anita; Sahlgren, B.; Johansson, Bo‐Lennart; Wahren, John

doi:10.1007/bf00403963

Cited by 149 publications

(186 citation statements)

References 44 publications

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“…However, consistent with previous studies from this laboratory and others [1][2][3]6], all C-peptidemodulated signalling events were inhibited by pertussis toxin, indicating that the signal is mediated via a G i -or G oprotein. The observed stimulation of the PI-3 kinase and Akt signalling pathway is not necessarily contradictory to the proposed G-protein involvement.…”

Section: Discussionsupporting

confidence: 91%

“…*p<0.05 vs control. A representative western blot image is shown in the upper panel of each graph Na + , K + -ATPase by this fragment [6,15,31,32], whereas scrambled C-peptide had no effect. In contrast to a previous study involving mouse endothelial cells [27], we did not observe an increase in p38 MAP kinase phosphorylation, which may be related to tissue-and speciesspecific differences.…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence to suggest that C-peptide binds to a G-protein-coupled membrane binding site on a number of different cell types [1], thereby triggering Ca 2+ -dependent intracellular signalling pathways [2] including the mitogen-activated protein (MAP) kinase cascade [3,4]. This results in subsequent activation of both Na + , K + -ATPase [5][6][7] and endothelial nitric oxide synthase (eNOS) [5][6][7][8]. Activation of these enzyme systems is of particular interest in diabetes, since both are reported to be deficient in this disorder [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…C-peptide also stimulates the phosphorylation of ERK1/2 and p38 MAP kinase in endothelial cells [27], resulting in increased eNOSmediated synthesis of NO and augmented formation of eNOS protein, secondary to upregulation of eNOS gene transcription, in rat aortic endothelial cells [8]. Moreover, C-peptide stimulates Na + , K + -ATPase activity [6] via PKC-α activation in rat medullary thick ascending limb cells [7]. However, a comprehensive picture of the sequential steps in the C-peptide signalling pathway has not been presented.…”

Section: Introductionmentioning

confidence: 99%

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C-peptide stimulates ERK1/2 and JNK MAP kinases via activation of protein kinase C in human renal tubular cells

et al. 2004

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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C-peptide stimulates ERK1/2 and JNK MAP kinases via activation of protein kinase C in human renal tubular cells

et al. 2004

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“…Na þ -K þ ATPase activity has been shown to be reduced in a variety of cell types in human and experimental IDDM [Wald et al, 1993;Gerbi et al, 1997]. C-peptide has been shown to stimulate Na þ -K þ ATPase activity in a number of tissues including erythrocytes and renal tubules in diabetic patients and animal models [Ohtomo et al, 1996;Dufayet et al, 1998;Forst et al, 2000]. Speculations are that decreased Na þ -K þ ATPase activity could directly cause an increase in vascular tone by increasing intracellular sodium and calcium in vascular smooth muscle [Forst et al, 2000].…”

Section: C-peptide and Its Biological Effectmentioning

confidence: 99%

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Joshua

Zhang

Falcone

et al. 2005

J of Cellular Biochemistry

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Complications associated with insulin-dependent diabetes mellitus (type-1diabetes) primarily represent vascular dysfunction that has its origin in the endothelium. While many of the vascular changes are more accountable in the late stages of type-1diabetes, changes that occur in the early or initial functional stages of this disease may precipitate these later complications. The early stages of type-1diabetes are characterized by a diminished production of both insulin and C-peptide with a significant hyperglycemia. During the last decade numerous speculations and theories have been developed to try to explain the mechanisms responsible for the selective changes in vascular reactivity and/or tone and the vascular permeability changes that characterize the development of type-1diabetes. Much of this research has suggested that hyperglycemia and/or the lack of insulin may mediate the observed functional changes in both endothelial cells and vascular smooth muscle. Recent studies suggest several possible mechanisms that might be involved in the observed decreases in vascular nitric oxide (NO) availability with the development of type-1 diabetes. In addition more recent studies have indicated a direct role for both endogenous insulin and C-peptide in the amelioration of the observed endothelial dysfunction. These results suggest a synergistic action between insulin and C-peptide that facilitates increase NO availability and may suggest new clinical treatment modalities for type-1 diabetes mellitus.

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Biological Effects of C‐peptide and Proinsulin

Wahren

Ekberg

Shafqat

et al. 2003

International Textbook of Diabetes Mellitus

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C‐peptide : In contrast to the earlier view, new data now indicate that proinsulin C‐peptide does exert important physiological effects and shows the characteristics of an endogenous peptide hormone. C‐peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G‐protein coupled receptor, resulting in subsequent activation of Ca 2+ ‐ and MAP‐kinase‐dependent signaling pathways. C‐peptide's binding to cell membranes is stereospecific and the C‐terminal pentapeptide segment participates in the process. Some studies indicate that C‐peptide and insulin may exert a synergistic effect on the insulin signaling pathway. C‐peptide stimulates Na + ,K + ‐ATPase and endothelial nitric oxide synthase activities. C‐peptide administration in replacement doses in animal models of diabetes or in type 1 diabetic patients results in increased blood flow in skeletal muscle, myocardium, kidney, nerve, and skin. C‐peptide replacement decreases glomerular hyperfiltration, reduces urinary albumin excretion, and corrects glomerular expansion. It also increases nerve conduction velocity, improves sensory nerve function, and reduces or reverses the characteristic diabetes‐induced nodal and paranodal nerve structural changes. The evidence suggests that replacement of C‐peptide together with insulin may be beneficial in patients with type 1 diabetes and serve to retard or prevent the development of long‐term complications. Proinsulin : Only a very small proportion of proinsulin is released in its intact form to the circulation in healthy subjects. In contrast, in type 2 diabetes, plasma proinsulin and its conversion intermediates may be higher than in healthy individuals. Proinsulin binds to the insulin receptor with approximately 10% of insulin's affinity. The suggestion of a specific effect of proinsulin in lowering hepatic glucose output has not been verified in direct studies. Clinical trials designed to evaluate the usefulness of proinsulin as an insulin analogue in type 2 diabetic patients were discontinued because of increased incidence of myocardial infarction. Recent reports of specific high affinity proinsulin receptors in several tissues are intriguing and warrant further investigation.

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C-peptide stimulates rat renal tubular Na+, K+-ATPase activity in synergism with neuropeptide Y

Cited by 149 publications

References 44 publications

C-peptide stimulates ERK1/2 and JNK MAP kinases via activation of protein kinase C in human renal tubular cells

C-peptide stimulates ERK1/2 and JNK MAP kinases via activation of protein kinase C in human renal tubular cells

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: Role of insulin and C‐peptide

Biological Effects of C‐peptide and Proinsulin

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