Direct Beneficial Effect of Insulin on Blood Rheologiacal Disorders in the Microcirculation

66Maya Mantskava, Nugzar Pargalava, 
George Mchedlishvili.

Microcirculation Research Center, I.Beritashvili Institure of Physiology, 14 Gotua St., 0160, Tbilisi, Georgia.
N, Bochua Center of Angiology and Vascular Surgery, 1. Chachava St., 0159, Tbilisi, Georgia.


Abstract. Under both in vivo and in vitro conditions we investigated effect on the most significant factor disturbing the blood rheological disorders in the microcirculation, the red blood cell aggregability. The in vivo studies we carried out in the 42 insulin treated diabetic patients (diabetes mellitus type II), as well as conducted the in vitro investigations of the blood both of the diabetic patients (24) and of the healthy people (20) where the insulin was added to the blood in vivo.
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The RBC aggregability in blood investigated with the “Georgian technique” was found significantly enhanced, by about 100 per cents in the diabetic patients. Under the in vivo conditions insulin administrated intravenously decreased the RBC aggregability almost to the normal level in diabetic patients. In addition, in vitro studies we found that the insulin lowered significantly the RBC aggregability when it was significantly enhanced by addition of Dextran-500, as well as in the blood of patients with the ischemic brain infarcts. The decreasing effect on the aggregability was observed even in the healthy control group where the RBC aggregability was in a normal range.[/su_animate]

1. Introduction

Numerous clinical data evidence those significant disturbances in the diabetic patients tissue are related just to the microvascular rheological disorders [1,4]. The most pronounced effect exhibits the RBCs aggregation, which increased during the brain infarcts by about 100 per cent, while the blood plasma viscosity, only by 10 per cents [3]. Taking into account the high significance of the problem from the diagnostic, pathogenic, and therapeutic points of view, we investigated the comparative effect of insulin on the RBC aggregability in diabetics.

2. Materials and methods

We investigated 67 patients with diabetes mellitus of type II (aged 42-67 years), 27 patients with brain infarcts (aged 51-78 years). As well as 25 healthy control volunteers (aged 35-51 years). The RBC aggregability was studied with the “Georgian technique” [2], which is direct, quantitative and more sensitive as compared to many others. In the in vitro conditions we added standard micro drops of 10 per cent Dexrtan-500 solution to the normal human blood. As to the Human Insulin Actrapid HM (Novo Nordisk, Denmark), it was added in an amount of 10-4 ml to 4 ml of the human blood. The results (M±δ) were treated statistically, the significance between the appropriate groups being determined with the differential technique.

Fig. 1. RBC aggregability in blood patients treated without and with insulin.

3. Results

Rbc aggregability in the out-patients with the type I of diabetes mellitus was found significantly increased (by mean 130 per cent) as compared to the healthy control group; However, this was not in evidence in the insulin treated patients (Fig.1). Comparable results were obtained in the healthy control group where the RBC aggregability was investigated in vitro following addition of high molecular Dextran-500: the aggregability index increased by ca. 135 per cent but lowered considerably following addition of insulin. Similar effect was observed also in the blood of patients with the cerebral insults where the RBC aggregability was considerably elevated (ca. 130 per cents as compared to the control) and decreased significantly after addition of insulin. It was also found that insulin decreased the RBC aggregability not only when it was elevated, but also when it remained in a normal range in the healthy probands: it decreased in this case to ca. 30 per cent as compared to the initial resting level.
4. Discussion

We found that insulin decreases the RBC aggregation not only in the in vivo but also under in vitro conditions, thus evidencing that the effect was undoubtedly direct and nothing to do with the carbohydrate metabolic disorders. In particular, this was in evidence after addition of the high molecular dextran to the healthy blood, in the blood of patients with the lacunars infarcts, and even in the blood of healthy probands where the RBC aggregability was in a normal range. Therefore, the reducing effect of insulin on the RBC aggregability is non-specific for the diabetes mellitus.


[1] G.Jorneskog and B. Fagrell. Discrepancy in skin capillary circu;lation between fingers and toes in patients with type I diabetes, Int. J. Microcirc. 16 (1996), 313-319.
[2] G. Mchedlishvili, N. Beritashvili, D. Lominadze, B. Tsinamdzgvrishvili. Technique for direct and quantitative evaluation of erythrocyte aggregability in blood samples. Biorheology. 30, (1993), 153-161
[3] G, Mchedlishvili, R. Shakarishvili, N. Momtselidze, L  Gobejishvili, M. Aloeva, M.  Mantskava. Comparative values of erythrocyte aggregability versus other indices of hemorheological disorders in patients with ischemic  brain infarct. Clin. Hemorheol. and Microcirc. 22, (2000),  9-15.
[4] N.Tanahashi, Y. Fukuuchi, M. Tomita, S. Matsouka amd H. Takead. Erythrocyte aggregability in patients with cerebral infarction with special reference to diabetes mellitus,. Biorheology 30 (1993), 253-259.


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