| 1. |
- Johansson, BL, et al.
(författare)
-
C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients
- 2004
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 286:1, s. E14-E19
-
Tidskriftsartikel (refereegranskat)abstract
- Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol·kg-1·min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 μg·kg-1·min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower ( P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion ( P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.
|
|
| 2. |
- Johansson, BL, et al.
(författare)
-
C-peptide increases forearm blood flow in patients with type 1 diabetes via a nitric oxide-dependent mechanism
- 2003
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 285:4, s. E864-E870
-
Tidskriftsartikel (refereegranskat)abstract
- Proinsulin C-peptide has been shown to increase muscle blood flow in type 1 diabetic patients. The underlying mechanism is not fully understood. The aim of this study was to evaluate if the vasodilator effect of C-peptide is mediated by nitric oxide (NO). Eleven type 1 diabetic patients were studied two times and randomized to administration of intravenous and intra-arterial infusion of C-peptide or saline. Forearm blood flow (FBF) was measured by venous occlusion plethysmography during infusion of C-peptide or saline before, during, and after NO synthase (NOS) blockade. Endothelium-dependent and -independent vasodilatation was evaluated by administration of acetylcholine and sodium nitroprusside, respectively. FBF increased by 35% during intravenous C-peptide ( P < 0.01) but not during saline infusion (–2%, not significant). NOS blockade resulted in a more pronounced reduction in FBF during intravenous C-peptide than during saline infusion (–41 vs. –26%, P < 0.05). Intra-arterial C-peptide failed to increase FBF during NOS blockade. However, when C-peptide was given after the recovery from NOS blockade, FBF rose by 30% ( P < 0.001). The vasodilator effects of acetylcholine and nitroprusside were not influenced by C-peptide. It is concluded that the stimulatory effect of C-peptide on FBF in type 1 diabetic patients is mediated via the NO system and that C-peptide increases basal endothelial NO levels.
|
|
| 3. |
- Wahren, J, et al.
(författare)
-
Role of C-peptide in human physiology
- 2000
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - 0193-1849. ; 278:5, s. E759-E768
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
- Yosten, GLC, et al.
(författare)
-
Physiological effects and therapeutic potential of proinsulin C-peptide
- 2014
-
Ingår i: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 307:11, s. E955-E968
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
