Decreased deformability of erythrocytes in hyperglycaemic non-inbred ob/ob mice

Abstract

The deformability of erythrocytes from non-inbred ob/ob mice and lean controls was analyzed by filtration through Nuclepore polycarbonate under constant pressure. At the age of 1-2 months there was no difference in erythrocyte filtrability between the two types of mice, whereas from 3 months the ob/ob mouse erythrocytes exhibited a markedly decreased deformability. The filtrability of erythrocytes was sensitive to osmotic pressure (NaCl or glucose). However, the difference between normal and ob/ob mouse erythrocytes was not due to acute osmotic effects of the hyperglycaemia in the ob/ob mice. When filtration was performed in the same glucose concentration as that recorded in the blood of the erythrocyte-donor animal, the difference in filtrability between adult normal and ob/ob mice remained large and significant (p less than 0.01). Moreover, the most pronounced hyperglycaemia occurred in young ob/ob mice with normal erythrocyte filtrability. It is suggested that non-inbred ob/ob mice are a useful model for studying the damaging influence of diabetes on erythrocyte deformability.

Insulin-driven erythropoiesis may underlie impairment of erythrocyte deformability in hyperinsulinaemic, hyperglycaemic ob/ob-mice

“…In addition, consistent with the decreased area-to-volume ratio of ob/ob-mouse erythrocytes, these cells lyzed more readily than control cells in hypo-osmolar buffer solutions. The impaired deformability, as reflected both in the subnormal osmotic resistance and in the previously reported decrease in filtrability through polycarbonate sieves [5,6], probably reflects the altered morphology of the ob/ob-mouse erythrocytes, even though other mechanisms may contribute.…”

“…In human diabetes mellitus the erythrocyte deformability is decreased [2][3][4]. A similar phenomenon has also been reported to occur in obese-hyperglycaemic (ob/ob) mice [5,6]. The abnormal rigidity of erythrocytes in diabetes may contribute to the development of vascular dysfunctions in capillaries [7] and larger vessels [8].…”

“…These ob/ob-mice are insulin resistant with a 10-100 fold increase in plasma insulin concentration and a hyperglycaemia that peaks in young animals and then gradually declines [5, 11], and have been widely used in exploring the mechanisms behind the stimulussecretion-coupling of insulin [14]. In terms of vascular complications these animals are characterized by certain glomerular lesions [15,16] as well as arteriolar abnormalities [17].…”

Blood glucose and stroke.

“…Poor prognosis in diabetics with stroke may be related to an increased incidence of cardiac death. Diabetics have chronic impairment of cerebral blood flow and autoregulation, 26 lower white and red blood cell deformability, 27 -29 hyperviscosity, 30 endothelial cell dysfunction, 31 hypercoagulability, 32 impaired prostacyclin synthesis that increases platelet adhesiveness, 33 -35 and possible dysfunction of cortical arteriolar smooth muscle and endothelium, 36 which are important for collateral flow. Alternatively, hyperglycemia, when present at the time of ischemia, may play a key role in infarct production and the outcome from ischemia in diabetics.…”

Combined use of micropipette aspiration and perifusion for studying red blood cell volume regulation

“…Many clinical disorders are linked with or caused by impaired RBC deformability, of which the coupling between increased blood pressure and impaired red cell volume regulation serves as an example of significant clinical importance (2,6). Red blood cell deformability is markedly affected by the ratio of cellular surface area to cellular volume [i.e., deformability decreases as the ratio becomes smaller; see (16)], yet the nonspherical shape of the RBC makes its geometry difficult to measure. Both surface area and volume can be determined via microscopy and partial aspiration of the RBC into a micropipette (23).…”