C‐peptide constricts pancreatic islet arterioles in diabetic, but not normoglycaemic mice

Nordquist, Lina; Lai, En Yin; Sjöquist, Mats; Jansson, Leif; Persson, Anna

doi:10.1002/dmrr.805

Cited by 6 publications

(3 citation statements)

References 8 publications

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“…When applied to healthy subjects, C-peptide did not affect forearm blood flow [14]. In in vitro studies, perfusion with C-peptide did not affect isolated islet arterioles from normoglycaemic mice [15]. The discrepancy might in part be explained by the fact that the C-peptide concentrations reached in the present study were most likely higher than the physiological interval of 0.5-3.0 nM.…”

contrasting

confidence: 69%

“…If so, a more widespread action of C-peptide on the vasculature in other organs, including the abundantly vascularized endocrine pancreas, might exist. To our knowledge, one recently published in vitro study demonstrated that mouse C-peptide induced constriction of pancreatic islet arterioles of diabetic mice but had no effect on normoglycaemic controls [15]. Furthermore, there is one previous in vivo study when C-peptide doses in the picomolar range failed to affect splanchnic blood flow [16].…”

Section: Introductionmentioning

confidence: 99%

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GLP-1, exendin-4 and C-peptide regulate pancreatic islet microcirculation, insulin secretion and glucose tolerance in rats

Olverling

Zhen

et al. 2011

Clinical Science

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GLP-1 (glucagon-like peptide 1) and its mimetic exendin-4 are used against Type 2 diabetes. C-peptide has also proven promising to enhance insulin action. Since insulin secretion in vivo can be rapidly tuned by changes in islet microcirculation, we evaluated the influence of GLP-1, exendin-4 and C-peptide on pancreatic IBF (islet blood flow), and dynamic changes in insulin secretion and glycaemia in the rat. Adult male Wistar rats were divided into four groups given intravenous saline, GLP-1, exendin-4 or C-peptide respectively and administered either saline or 30% glucose. Furthermore, we investigated the effect of intravenous infusion of different doses of exendin-4 into either the femoral vein or the portal vein on islet microcirculation. A non-radioactive microsphere technique was adopted to measure the regional blood flow. Both GLP-1 and exendin-4 prevented the glucose-induced PBF (pancreatic blood flow) redistribution into the islets. Infusion of exendin-4 into the portal vein did not alter pancreatic islet microcirculation, while infusion of exendin-4 into femoral vein significantly decreased basal IBF. C-peptide increased basal IBF and the proportion of IBF out of total PBF, but did not affect the islet microcirculation after glucose administration. GLP-1, exendin-4 and C-peptide stimulated insulin secretion and significantly decreased glycaemia. Blocking NO formation did not prevent the decreased IBF and post-load glycaemia evoked by exendin-4, but further decreased IBF and KBF (kidney blood flow) and increased basal glycaemia. Blocking the vagus nerve enhanced pancreatic IBF and further decreased post-load glycaemia and KBF and increased basal glycaemia. The vascular modulatory effect on pancreatic islet microcirculation described herein, with subsequent effects on in vivo insulin secretion and glycaemia, might be one of the mechanisms underlying the anti-diabetic actions of GLP-1 and its long acting mimetic exendin-4, as well as that of C-peptide.

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contrasting

confidence: 69%

Section: Introductionmentioning

confidence: 99%

GLP-1, exendin-4 and C-peptide regulate pancreatic islet microcirculation, insulin secretion and glucose tolerance in rats

Olverling

Zhen

et al. 2011

Clinical Science

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“…Shortly after induction of diabetes in lambs, coronary vascular resistance is elevated (Lee and Downing 1979), and diabetic animals are prone to develop increased total peripheral resistance and hypertension (Bell et al 2006). Administration of C-peptide restores diabetes-impaired skeletal muscle perfusion (Johansson et al 1992a), improves capillary skin red blood cell velocity (Forst et al 1998), and myocardial blood perfusion (Hansen et al 2002) as well as pancreatic islet arteriole diameter (Nordquist et al 2008b). In type 2 diabetes, C-peptide concentrations correlate with the presence of coronary artery disease and peripheral vascular disease (Sari and Balci 2005).…”

Section: Beneficial Effects Of C-peptidementioning

confidence: 99%

Renal and vascular benefits of C-peptide: Molecular mechanisms of C-peptide action

Nordquist

Palm²,

Andresen³

2008

BTT

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C-peptide has long been thought to be an inert byproduct of insulin production, but it has become apparent, and accepted, that C-peptide has important biological properties. C-peptide displays beneficial effects in many tissues affected by diabetic complications, such as increased peripheral blood flow and protection from renal damage. However, the mechanisms mediating these effects remain unclear. C-peptide interacts with cellular membranes at unidentified sites distinctive of the insulin family of receptors, and signals to multiple targets known to play a role in diabetes and diabetic complications, such as Na+/K+-ATPase and NOS. In general, the physiological and molecular effects of C-peptide resemble insulin, but C-peptide also possesses traits separate from those of insulin. These basic studies have been confirmed in human studies, suggesting that C-peptide may lend itself to clinical applications. However, the molecular and physiological properties of C-peptide are not completely elucidated, and large clinical studies have not begun. In order to further these goals, we critically summarize the current state of knowledge regarding C-peptide’s renal and vascular effects and the molecular signaling of C-peptide.

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Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans

Jansson

Carlsson

2019

Comprehensive Physiology

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The pancreatic islets are more richly vascularized than the exocrine pancreas, and possess a 5‐ to 10‐fold higher basal and stimulated blood flow, which is separately regulated. This is reflected in the vascular anatomy of the pancreas where islets have separate arterioles. There is also an insulo‐acinar portal system, where numerous venules connect each islet to the acinar capillaries. Both islets and acini possess strong metabolic regulation of their blood perfusion. Of particular importance, especially in the islets, is adenosine and ATP/ADP. Basal and stimulated blood flow is modified by local endothelial mediators, the nervous system as well as gastrointestinal hormones. Normally the responses to the nervous system, especially the parasympathetic and sympathetic nerves, are fairly similar in endocrine and exocrine parts. The islets seem to be more sensitive to the effects of endothelial mediators, especially nitric oxide, which is a permissive factor to maintain the high basal islet blood flow. The gastrointestinal hormones with pancreatic effects mainly influence the exocrine pancreatic blood flow, whereas islets are less affected. A notable exception is incretin hormones and adipokines, which preferentially affect islet vasculature. Islet hormones can influence both exocrine and endocrine blood vessels, and these complex effects are discussed. Secondary changes in pancreatic and islet blood flow occur during several conditions. To what extent changes in blood perfusion may affect the pathogenesis of pancreatic diseases is discussed. Both type 2 diabetes mellitus and acute pancreatitis are conditions where we think there is evidence that blood flow may contribute to disease manifestations. © 2019 American Physiological Society. Compr Physiol 9:799‐837, 2019.

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C‐peptide constricts pancreatic islet arterioles in diabetic, but not normoglycaemic mice

Abstract: These findings suggest a role for C-peptide in the regulation of islet blood flow, especially during conditions with impaired glucose tolerance.

Cited by 6 publications

References 8 publications

GLP-1, exendin-4 and C-peptide regulate pancreatic islet microcirculation, insulin secretion and glucose tolerance in rats

GLP-1, exendin-4 and C-peptide regulate pancreatic islet microcirculation, insulin secretion and glucose tolerance in rats

Renal and vascular benefits of C-peptide: Molecular mechanisms of C-peptide action

Pancreatic Blood Flow with Special Emphasis on Blood Perfusion of the Islets of Langerhans

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