慢性肾功能衰竭患者红细胞变形能力与红细胞ATP酶活性及离子浓度…

检测６５例ＣＲＦ患者ＥＤ和红细胞ＡＴＰ酶活性离子浓度的变化。结果显示；ＣＲＦ患者红细胞滤过指数和Ｃａ＾２＋，Ｎａ＾＋明显高于对照组，而Ｎａ＾＋、Ｋ＾＋－ＡＴＰ酶Ｃａ＾２＋－Ｍｇ＾２＋－ＡＴＰ酶活性和Ｋ＾＋、Ｍｇ＾２＋明显低于对照组。ＣＲＦ患者ＩＦ与Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶、Ｃａ＾２＋－Ｍｇ＾２＋－ＡＴＰ酶活性和Ｋ＾＋、Ｍｇ＾２＋浓度呈负相关，与Ｃａ＾２＋、Ｎａ＾＋浓度呈相关。     

红细胞膜Na~+-K~+-ATP酶活性与动脉硬化性脑梗塞的关系

为探讨红细胞膜Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶活性与动脉硬化性脑梗塞的关系，本文检测了３７例动脉硬化性脑梗塞患者、２０例脑动脉硬化症患者和２５例健康对照者的红细胞膜Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶活性，并将酶活性与脑ＣＴ梗塞灶大小进行直线回归分析。结果发现，动脉硬化性脑梗塞和脑动脉硬化症患者的Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶活性明显降低，酶活性降低程度与脑ＣＴ梗塞灶大小呈显著负相关性（ｒ＝－０．５８，Ｐ〈０．０１）     

糖尿病患者红细胞膜磷脂成分与Na~＋－K~＋－ATP酶活性的变化

探讨了ＮＩＤＤＭ患者红细胞膜磷脂成分与Ｎａ＋－Ｋ＋－ＡＴＰ酶活性的变化。结果：ＮＩＤＤＭ患者红细胞膜甘油磷脂及神经鞘磷脂显著降低，溶血磷脂酰胆碱显著增高；红细胞膜Ｎａ＋－Ｋ＋－ＡＴＰ酶及Ｍｇ＋＋－ＡＴＰ酶活性降低，且红细胞膜磷脂成分改变与酶活性降低显著相关。提示ＮＩＤＤＭ患者红细胞膜磷脂成分改变对膜Ｎａ＋－Ｋ＋－ＡＴＰ酶与Ｍｇ＋＋－ＡＴＰ酶活性有明显影响，并且它们都可能参与糖尿病视网膜病变的发生。     

槲皮素对糖尿病大鼠坐骨神经Na~＋－K~＋－ATP酶活力的影响

应用槲皮素（１００ｍｇ·ｋｇ－１／ｄ）对糖尿病大鼠灌胃治疗４周。结果发现治疗后糖尿病大鼠坐骨神经山梨醇含量明显下降，同时Ｎａ＋－Ｋ＋－ＡＴＰ酶活力明显增高，但肌醇含量无明显变化。提示槲皮素能纠正糖尿病神经组织山梨醇代谢的异常，改善Ｎａ＋－Ｋ＋－ＡＴＰ酶的活力。     

大蒜素对糖尿病小鼠脏器ATP酶的保护作用

观察糖尿病小鼠脏器ＡＴＰ酶活性的变化及大蒜素对其的影响，结果显示，糖尿病小鼠心、脑、脾、肾、肝线粒体及微粒体Ｎａ＾＋－Ｋ＾＋－ＡＴＰ酶、Ｃａ＾２＋－ＡＴＰ酶活性明显下降或呈下降趋势，大蒜素能有效提高各脏器ＡＴＰ酶活性，提示大蒜素对糖尿病及其并发症防治具有重要意义。     

氦氖激光血管内照射对糖尿病患者红细胞变形能力和Na~ -K~ -ATP酶的影响

目的　观察低能量氦氖激光血管内照射（ＩＬＩＢ）对 ２型糖尿病患者红细胞变形能力（ＲＢＣＤ）和Ｎａ＋－Ｋ＋－ＡＴＰ酶的影响。方法９８例糖尿病患者应用 ＩＬＩＢ治疗,每日１次,每次６０ｍｉｎ,检测治疗前后 ＲＢＣＤ和红细胞 Ｎａ＋－ Ｋ＋－ ＡＴＰ酶活性。结果 ２型糖尿病患者 ＲＢＣＤ及红细胞 Ｎａ＋－ Ｋ＋－ ＡＴＰ酶的活性较正常对照组均明显减低,而各糖尿病组经激光治疗１０ｄ后,其ＲＢＣＤ及Ｎａ＋－Ｋ＋－ＡＴＰ酶活性较治疗前有明显提高（Ｐ＜０．０５）。结论ＩＬＩＢ可提高２型糖尿病患者ＲＢＣＤ及红细胞Ｎａ＋－Ｋ＋－ＡＴＰ酶活性。     

慢性肾功能衰竭患者红细胞变形能力与红细胞ATP酶活性及离子浓度关系的研究

检测６５例ＣＲＦ患者ＥＤ和红细胞ＡＴＰ酶活性及离子浓度的变化。结果显示：ＣＲＦ患者红细胞滤过指数（ＩＦ）和Ｃａ２＋，Ｎａ＋明显高于对照组（Ｐ＜０．００１），而Ｎａ＋－Ｋ＋－ＡＴＰ酶、Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶活性和Ｋ＋，Ｍｇ２＋明显低于对照组（Ｐ＜０．００１）。ＣＲＦ患者ＩＦ与Ｎａ＋－Ｋ＋－ＡＴＰ酶、Ｃａ２＋－Ｍｇ２＋－ＡＴＰ酶活性和Ｋ＋、Ｍｇ２＋浓度呈负相关，与Ｃａ２＋、Ｎａ＋浓度呈正相关。提示ＣＲＦ患者ＥＤ降低与红细胞ＡＴＰ酶活性降低和离子浓度异常有关。     

糖尿病患者Na~＋－K~＋－ATP酶活性降低和血浆溶血磷脂酰胆碱浓度

０６２　糖尿病患者Ｎａ￣＋－Ｋ￣＋－ＡＴＰ酶活性降低和血浆溶血磷脂酰胆碱浓度［英］／ＲａｂｉｎｉＲＡ…∥Ｄｉａｂｅｔｅｓ．－１９９４，４３（７）．－９１５～９１９有研究报道糖尿病和高血压病等能引起血浆膜Ｎａ＋－Ｋ＋－ＡＴＰ酶活性降低，并推测钠离子主动...     

大黄抑制近端小管和髓袢升支粗段小管Na~＋－K~＋ATP酶活性

在体内和体外实验中系统地观察了中药大黄对大鼠近端小管和髓袢升支粗段小管Ｎａ￣＋－ｋ￣＋ＡＴＰ酶活性的影响，发现大黄对此二节段肾小管Ｎａ￣＋－Ｋ￣＋ＡＴＰ酶均具有显著抑制作用，尤其是对髓袢升支粗段作用更为明显。大黄的作用随剂量增大而增强，５０ｍｇ／Ｌ大黄对髓袢升支粗段Ｎａ￣＋Ｋ￣＋ＡＴＰ酶活性的抑制率达４２．９％。体内应用大黄后，出现利钠、利尿效应。本实验结果进一步明确了大黄对残余肾肾小管高代谢的抑制作用。     

原发性高血压Ca^2＋—ATP酶活性改变及光量子治疗对其影响

测定了３０例原发性高血压和３０例正常对照组红细胞膜Ｃａ＾２＋－ＡＴＰ酶活性，并用光量子治疗原发性高血压后观察其红细胞膜Ｃａ＾２＋－ＡＴＰ酶活性改变。结果：高血压病组红细胞膜Ｃａ＾２＋－ＡＴＰ酶活性较对照组降低（Ｐ〈０．０１），而经光量子治疗血压下降后，Ｃａ＾２＋－ＡＴＰ酶活性明显升高（Ｐ〈０．０１）。提示Ｃａ＾２＋－ＡＴＰ酶活性降低可能为原发性高血压的发病机制之一，而光量子治疗高血压的机制可能与其     

Genetic and environmental regulation of Na/K adenosine triphosphatase activity in diabetic patients

Even if the pathogenesis of diabetic neuropathy is incompletely understood, an impaired Na/K adenosine triphosphatase (ATPase) activity has been involved in this pathogenesis. We previously showed that a restriction fragment length polymorphism (RFLP) of the ATP1-A1 gene encoding for the Na/K ATPase's alpha 1 isoform is associated with a low Na/K ATPase activity in the red blood cells (RBCs) of type 1 diabetic patients. We thus suggested that the presence of the variant of the ATP1A1 gene is a predisposing factor for diabetic neuropathy, with a 6.5% relative risk. Furthermore, there is experimental evidence showing that lack of C-peptide impairs Na/K ATPase activity, and that this activity is positively correlated with C-peptide level. The aim of this study was to evaluate the respective influence of genetic (ATP1-A1 polymorphism) and environmental (lack of C-peptide) factors on RBC's Na/K ATPase activity. Healthy and diabetic European and North African subjects were studied. North Africans were studied because there is a high prevalence and severity of neuropathy in this diabetic population, and ethnic differences in RBC's Na/K ATPase activity are described. In Europeans, Na/K ATPase activity was significantly lower in type 1 (285 +/- 8 nmol Pi/mg protein/h) than in type 2 diabetic patients (335 +/- 13 nmol Pi/mg protein/h) or healthy subjects (395 +/- 9 nmol Pi/mg protein/h). Among type 2 diabetic patients, there was a significant correlation between RBC's Na/K ATPase activity and fasting plasma C-peptide level (r = 0.32, P <.05). In North Africans, we confirm the ethnic RBC's Na/K ATPase activity decrease in healthy subjects (296 +/- 26 v 395 +/- 9 nmol Pi/mg protein/h, r < 0.05), as well as in type 1 diabetic patients (246 +/- 20 v 285 +/- 8 nmol Pi/mg protein/h; P <.05). However, there is no relationship between the ATP1A1 gene polymorphism and Na/K ATPase activity. ATP1A1 gene polymorphism could not explain the ethnic difference. We previously showed that Na/K ATPase activity is higher in type 1 diabetic patients without the restriction site on ATP1A1 than in those heterozygous for the restriction site. This fact was not observed in healthy subjects. In type 2 diabetic patients, association between ATP1A1 gene polymorphism and decreased enzyme activity was found only in patients with a low C-peptide level. Therefore, the ATP1-A1 gene polymorphism influences Na/K ATPase activity only in case of complete or partial C-peptide deficiency, as observed in type 1 and some type 2 diabetic patients, without any correlation with hemoglobin A1c (HbA1c). Correlation observed between C-peptide levels and RBC's Na/K ATPase suggests that the deleterious effect of C peptide deficiency on Na/K ATPase activity is worse in the presence of the restriction site. This may explain the high relative risk of developing the neuropathy observed in type 1 diabetic patients bearing the variant allele.     

Reduction of erythrocyte (Na(+)-K+) ATPase activities in non-insulin-dependent diabetic patients with hyperkalemia.

To elucidate the mechanism of hyperkalemia in diabetic patients without renal failure, we investigated (Na(+)-K+) adenosine triphosphatase (ATPase) activity in erythrocyte membrane, erythrocyte Na+ and K+ content, and plasma endogenous digitalis-like substance in control subjects (n = 16) and non-insulin-dependent diabetes mellitus (NIDDM) patients (n = 62). NIDDM patients were divided into normokalemic patients (NKDM, n = 48) and hyperkalemic patients (HKDM, n = 14). There was no difference in plasma glucose or hemoglobin A1c (HbA1c) levels, plasma renin activity (PRA), and plasma aldosterone concentrations (PAC) between NKDM and HKDM patients. (Na(+)-K+)ATPase activities in NIDDM patients were significantly reduced compared with those in control subjects (0.336 +/- 0.016 mumol-inorganic phosphate [Pi]/mg protein/h, mean +/- SEM, P less than .05), and (Na(+)-K+)ATPase activities in HKDM patients (0.243 +/- 0.015 mumol Pi/mg protein/h) were significantly reduced compared with those in NKDM patients (0.295 +/- 0.008 mumol Pi/mg protein/h, P less than .01). Plasma K+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in diabetic patients (r = -.365, P less than .01). Erythrocyte Na+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in control subjects (r = -.619, P less than .05). There was no difference in plasma endogenous digitalis-like substance among the three groups. (Na(+)-K+)ATPase activity was not significantly correlated with plasma endogenous digitalis-like substance in control subjects and diabetic patients. These findings suggest that the reduction of (Na(+)-K+)ATPase activity, which was not related to plasma digitalis-like substance, may be partly responsible for hyperkalemia in diabetic patients.     

Relationship between neuropathy, hypertension and red blood cell Na/K ATPase in patients with insulin-dependent diabetes mellitus.

Hypertension has been proposed as an independent risk factor for diabetic neuropathy. In insulin-dependent diabetic (IDDM) patients suffering from neuropathy, red blood cell (RBC) Na/K ATPase is decreased. Such a decrease might be involved in the physiopathology of hypertension and therefore be the link between hypertension and neuropathy. To confirm this hypothesis, we studied 104 IDDM patients with a long duration of disease by looking at the association between neuropathy and hypertension and by comparing RBC Na/K ATPase activity in subgroups. The independent risk factors associated with neuropathy were hypertension, triglyceride level, diabetes duration and low RBC Na/K ATPase activity. Contrary to our expectations, Na/K ATPase was not decreased in hypertensive patients (294 +/- 16 nmol Pi/mg prot/h vs 303 +/- 9), but those treated with angiotensin converting enzyme (ACE) inhibitor had higher RBC Na/K ATPase activity than those treated with calcium blockers (355 +/- 15 nmol Pi/mg prot/h vs 216 +/- 10). These results confirm the association between neuropathy and hypertension, on the one hand, and neuropathy and decreased Na/K ATPase, on the other, and show that hypertension in IDDM patients was not associated with decreased RBC Na/K ATPase. Moreover, ACE inhibitor treatment in IDDM patients, whether hypertensive or not, was associated with higher levels of RBC Na/K ATPase, which could account for its beneficial effect on diabetic neuropathy.     

Changes in (Na++K+)ATPase Activity and the Composition of Surface Carbohydrates in Erythrocyte Membranes in Alcoholics

(Na+ + K+)ATPase activity and sensitivity to the inhibitory effect of ethanol and noradrenaline in vitro as well as the concentrations of sialic acid, galactose, and hexosamine were determined in erythrocyte membranes in 20 healthy controls and in 20 alcoholic patients within 24 hr of withdrawal. Basal (Na+ + K+)ATPase activity, the sensitivity of the enzyme to inhibition by ethanol and noradrenaline added in vitro, and the concentrations of sialic acid and galactose were significantly reduced in the patients (p less than 0.0005). All of these abnormalities were significantly correlated to each other as well as to the estimated daily quantity of ethanol consumed. After enzymatic removal of terminal sialic acid and terminal and sialic acid-bound beta-galactose, the (Na+ + K+)ATPase differences between the patients and the controls were eliminated. The results showed that the previously reported reduced inhibition of (Na+ + K+)ATPase by ethanol in the presence of noradrenaline in brain membranes in chronically ethanol-fed animals is also found in erythrocyte membranes in alcoholic humans. Abnormal carbohydrate composition of glycolipids and/or glycoproteins of the membrane surface appeared to be related to the (Na+ + K+)ATPase changes, possibly due to interference either with K+ transport or surface electrostatics or, directly or indirectly, with the conformation of (Na+ + K+)ATPase.     

Blood pressure, erythrocyte sodium and potassium concentrations and Na+K+ATPase activity in children with hypertensive mothers

Fifty-four children aged 10-15 years were studied. Twenty-two children had mothers who had sustained hypertension after a hypertensive pregnancy (HT) and 17 had normotensive mothers who had previously had a hypertensive pregnancy (NT). A control group consisted of 15 children with normotensive mothers (C). Blood pressure was significantly higher in the HT group in comparison with the C group (P less than 0.01). Erythrocyte sodium (Na+) and potassium (K+) concentrations were similar in all groups and not related to blood pressure. The Na+K+ATPase activity in erythrocyte membranes was lower in the HT group than in the NT group (P less than 0.02), but not significantly different from the C group. There was no statistically significant correlation between Na+K+ATPase activity and blood pressure.     

C-peptide, Na+,K(+)-ATPase, and diabetes

Na+,K(+)-ATPase is an ubiquitous membrane enzyme that allows the extrusion of three sodium ions from the cell and two potassium ions from the extracellular fluid. Its activity is decreased in many tissues of streptozotocin-induced diabetic animals. This impairment could be at least partly responsible for the development of diabetic complications. Na+,K(+)-ATPase activity is decreased in the red blood cell membranes of type 1 diabetic individuals, irrespective of the degree of diabetic control. It is less impaired or even normal in those of type 2 diabetic patients. The authors have shown that in the red blood cells of type 2 diabetic patients, Na+,K(+)-ATPase activity was strongly related to blood C-peptide levels in non-insulin-treated patients (in whom C-peptide concentration reflects that of insulin) as well as in insulin-treated patients. Furthermore, a gene-environment relationship has been observed. The alpha-1 isoform of the enzyme predominant in red blood cells and nerve tissue is encoded by the ATP1A1 gene. A polymorphism in the intron 1 of this gene is associated with lower enzyme activity in patients with C-peptide deficiency either with type 1 or type 2 diabetes, but not in normal individuals. There are several lines of evidence for a low C-peptide level being responsible for low Na+,K(+)-ATPase activity in the red blood cells. Short-term C-peptide infusion to type 1 diabetic patients restores normal Na+,K(+)-ATPase activity. Islet transplantation, which restores endogenous C-peptide secretion, enhances Na+,K(+)-ATPase activity proportionally to the rise in C-peptide. This C-peptide effect is not indirect. In fact, incubation of diabetic red blood cells with C-peptide at physiological concentration leads to an increase of Na+,K(+)-ATPase activity. In isolated proximal tubules of rats or in the medullary thick ascending limb of the kidney, C-peptide stimulates in a dose-dependent manner Na+,K(+)-ATPase activity. This impairment in Na+,K(+)-ATPase activity, mainly secondary to the lack of C-peptide, plays probably a role in the development of diabetic complications. Arguments have been developed showing that the diabetes-induced decrease in Na+,K(+)-ATPase activity compromises microvascular blood flow by two mechanisms: by affecting microvascular regulation and by decreasing red blood cell deformability, which leads to an increase in blood viscosity. C-peptide infusion restores red blood cell deformability and microvascular blood flow concomitantly with Na+,K(+)-ATPase activity. The defect in ATPase is strongly related to diabetic neuropathy. Patients with neuropathy have lower ATPase activity than those without. The diabetes-induced impairment in Na+,K(+)-ATPase activity is identical in red blood cells and neural tissue. Red blood cell ATPase activity is related to nerve conduction velocity in the peroneal and the tibial nerve of diabetic patients. C-peptide infusion to diabetic rats increases endoneural ATPase activity in rat. Because the defect in Na+,K(+)-ATPase activity is also probably involved in the development of diabetic nephropathy and cardiomyopathy, physiological C-peptide infusion could be beneficial for the prevention of diabetic complications.     

The effects ex vivo and in vitro of insulin and C-peptide on Na/K adenosine triphosphatase activity in red blood cell membranes of type 1 diabetic patients

The decrease in Na/K adenosine triphosphatase (ATPase) activity observed in several tissues of type 1 diabetic patients is thought to play a role in the development of long-term complications. Infusion of insulin may restore this enzyme activity in red blood cells (RBCs), and recent arguments have been developed for a similar role of C-peptide. The aims of this study were to determine whether insulin acts directly on the RBC enzyme and to evaluate the effect of C-peptide on Na/K ATPase activity. Thirty-nine C-peptide-negative type 1 diabetic patients were studied (blood glucose, 11.2 +/- 1.49 mmol/L; hemoglobin A1c [HbA1c], 8.9% +/- 0.1%, mean +/- SEM). Blood samples were obtained in the morning, before breakfast and insulin injection. Intact and living RBCs were resuspended in their own plasma and incubated with or without insulin (50 microU/mL) or C-peptide (6 nmol/L). Ex vivo by microcalorimetry, the heat produced after 1 hour by the enzyme-induced hydrolysis of adenosine triphosphate (ATP), was measured in a thermostated microcalorimeter at 37 degrees C. The results showed that Na/K ATPase activity was significantly increased by insulin (12.4 +/- 0.5 v 15.4 +/- 0.9 mW/L RBCs, P < .05, n = 23) but not by C-peptide (11.9 +/- 0.7 v 12.9 +/- 0.9 mW/L RBCs, NS, P = .26, n = 12). In another experiment, RBC suspensions were incubated at 37 degrees C in a water bath with or without insulin (50 microU/mL) or C-peptide (6 nmol/L) for 10 minutes. RBC membranes were isolated and Na/K ATPase activity was assessed by measuring inorganic phosphate release at saturating concentrations of all substrates. The results showed that insulin and C-peptide significantly increased RBC Na/K ATPase activity (342 +/- 25, P < .005 and 363 +/- 30, P < .005, respectively v255 +/- 22 nmol Pi x mg protein(-1) x h(-1), n = 14). We conclude that insulin and C-peptide act directly on RBC Na/K ATPase, thus restoring this activity in type 1 diabetic patients. The stimulatory effect of C-peptide observed in vitro on RBC Na/K ATPase activity confirms that C-peptide plays a physiological role.     

Effect of age on red cell membrane sodium -potassium dependent adenosine triphosphatase (Na+-K+ ATPase) activity in healthy men

Decreased cellular thermogenesis may represent a normal aspect of the aging process. Whereas Na+-K+ ATPase appears to be involved directly in body metabolism, enzyme activity on the erythrocyte membrane Na+-K+ ATPase was significantly lower in aged men. In a separate series of experiments, each with representation from the two age groups, red cell membrane Na+-K+ ATPase was also found to be decreased significantly in the aged men. Although mean values were statistically different, one of the elderly men had enzyme activity above that of the mean of the younger men. None of the younger men had enzyme activity below the mean of the older group. Red cell membrane Na+-,+ ATPase activity may be an indicator of physiological aging.     

(Na+ + K+) ATPase inhibitors and intracellular electrolytes in essential hypertension

White blood cell (WBC) Na+ and K+ concentrations, plasma (Na+ + K+)ATPase inhibition and blood pressure were determined in normotensive control subjects and patients with essential hypertension. While the untreated hypertensive group had significantly lower WBC K+ concentrations than the normotensive group (mean +/- SEM, 121.6 +/- 4.4 vs. 134.7 +/- 2.8 mEq/kg, p less than 0.05), no significant difference was observed in WBC Na+ concentrations between the 2 groups. The mean of plasma (Na+ + K+)-ATPase inhibition in untreated hypertensive patients was higher than that in normotensive controls (14.8 +/- 1.7 vs. 7.2 +/- 1.8%, p less than 0.05). The correlations between (Na+ + K+)ATPase inhibition and mean blood pressure and between WBC Na+/K+ ratio and mean blood pressure were significant (r = 0.278, p less than 0.05 and 0.270, p less than 0.05, respectively), but both were weak. However, untreated hypertensive patients with higher (Na+ + K+)ATPase inhibition had significantly higher WBC Na+/K+ ratios than untreated patients with less (Na+ + K+)ATPase inhibition. These results suggest a contribution of plasma (Na+ + K+)ATPase inhibition in the production of high blood pressure in a subset of patients with essential hypertension, which results in altered intracellular K+ concentrations.     

Effects of C-peptide on microvascular blood flow and blood hemorheology

Beside functional and structural changes in vascular biology, alterations in the rheologic properties of blood cells mainly determines to an impaired microvascular blood flow in patients suffering from diabetes mellitus. Recent investigations provide increasing evidence that impaired C-peptide secretion in type 1 diabetic patients might contribute to the development of microvascular complications. C-peptide has been shown to stimulate endothelial NO secretion by activation of the Ca2+ calmodolin regulated enzyme eNOS. NO himself has the potency to increase cGMP levels in smooth muscle cells and to activate Na+K+ATPase activity and therefore evolves numerous effects in microvascular regulation. In type 1 diabetic patients, supplementation of C-peptide was shown to improve endothelium dependent vasodilatation in an NO-dependent pathway in different vascular compartments. In addition, it could be shown that C-peptide administration in type 1 diabetic patients, results in a redistribution of skin blood flow by increasing nutritive capillary blood flow in favour to subpapillary blood flow. Impaired Na+K+ATPase in another feature of diabetes mellitus in many cell types and is believed to be a pivotal regulator of various cell functions. C-peptide supplementation has been shown to restore Na+K+ATPase activity in different cell types during in vitro and in vivo investigations. In type 1 diabetic patients, C-peptide supplementation was shown to increase erythrocyte Na+K+ATPase activity by about 100%. There was found a linear relationship between plasma C-peptide levels and erythrocyte Na+K+ATPase activity. In small capillaries, microvascular blood flow is increasingly determined by the rheologic properties of erythrocytes. Using laser-diffractoscopie a huge improvement in erythrocyte deformability could be observed after C-peptide administration in erythrocytes of type 1 diabetic patients. Inhibition of the Na+K+ATPase by Obain completely abolished the effect of C-peptide on erythrocyte deformability. In conclusion, C-peptide improves microvascular function and blood flow in type 1 diabetic patients by interfering with vascular and rheological components of microvascular blood flow.