In order to assess the participation of the microfilamentous cell web in the multiphasic response of the pancreatic beta cell, the effect of cytochalasin B upon both glucose- and sulfonylurea-induced insulin release was investigated in the perfused isolated pancreas. Cytochalasin B failed to affect the basal rate of insulin release, but enhanced the initial and later phases of insulin secretion in response to either glucose or gliclazide. In addition, cytochalasin B lowered the threshold concentration for the stimulant action of glucose upon insulin release. Ultrastructural studies supported the concept of a specific interaction of cytochalasin B with the microfilamentous cell web of the beta cell. It is concluded that the integrity of such a structure is equally important for both the initial and later secretory responses of the beta cell to various insulinotropic agents.

Animals↗

PubMedDate not supplied

Calcium antagonists and islet function. IX. Is extracellular calcium required for insulin release?

The physiological relevance of extracellular Ca2+ and Mg2+ to the process of glucose-induced insulin release is examined in both the isolated perfused rat pancreas and rat isolated pancreatic islets. When no Ca2+ is added to the perfusion or incubation media, both the initial and late phases of insulin release are severely impaired. The effect of Ca2+ deprivation is an immediate and immediately reversible phenomenon, although the length of the period of Ca2+ deprivation prior to stimulation with glucose modulates the severity of the impairment in the secretory response. When Mg2+ is omitted from the media, the response to glucose occurs precociously and at a higher than normal rate, such a facilitation being a rapid phenomenon. When both Ca2+ and Mg2+ are removed from the extracellular milieu, the secretory response may occur in a normal fashion, except for an earlier onset. The rate of secretion is only reduced after or during a prolonged exposure of the endocrine pancreas to media deprived of both Ca2+ and Mg2+. The release of insulin evoked by glucose in the absence of Ca2+ and Mg2+ is enhanced by theophylline, partially inhibited by verapamil, and abolished by the Ca2+-chelator EGTA. It is concluded that Mg2+, in physiological concentration, exerts an inhibitory effect upon the process of glucose-induced insulin release. However, even in the absence of extracellular Mg2+, the secretory process remains apparently dependent on the availability of minute amounts of extracellular Ca2+.

Animals↗

PubMedDate not supplied

The stimulus-secretion coupling of glucose-induced insulin release XIX. The insulinotropic effect of glyceraldehyde.

Glyceraldehyde is known to stimulate insulin release. Its influence on various parameters of islet function was investigated in order to assess the possible significance of glycolsis in the insulinotropic action of glucose. In the absence of glucose, glyceraldehyde (5-20 mM), but neither dihydroxyacetone nor glycerol stimulated insulin release in rat isolated islets. The glucose-like effect glyceraldehyde (10 mM) was characterized by a shift to the left of the curve relating insulin release to glucose concentration, without any significant increase in the maximal velocity of the secretory process. In the isolated perfused rat pancreas, glyceraldehyde provoked a biphasic secretory response. Glyceraldehyde-induced insulin release was inhibited in the absence of calcium or in the presence of epinephrine, unaffected by mannoheptulose or 3,3-tetramethyleneglutaric acid, and enhanced by theophylline and cytochalism B. Glyceraldehyde also stimulated to pro-insulin biosynthesis and 45Ca net uptake by isolated islets, the latter effect being apparently due, in part at least, to inhibition of calcium outward transport across the cell membrane. At concentrations of nearly equivalent insulinotropic potency, glucose and glyceraldehyde were metabolized at rates yielding comparable output of both lactate and 14CO2. The data indicate that glyceraldehyde mimics many effects of glucose on islet function, suggesting that the insulinotropic action of glucose may be related to its metabolism through the glycolytic pathway.

Animals↗

PubMedDate not supplied

Blood glycogen and metabolic control in diabetes mellitus.

The relationship between metabolic control and leukocyte glycogen content in diabetes mellitus was re-evaluated, blood glycogen being measured by an enzymatic procedure. In 30 healthy subjects, fasting blood glycogen averaged 50.6 +/- 2.8 mg l-1 or 7.45 +/- 0.42 ng 10(3)-cells-1, the latter value being unaffected during a 60-min period of induced hyperglycaemia. Comparable levels were found in 18 Type 1 insulin-treated diabetic patients (blood glycogen 50.4 +/- 4.6 mg l-1, leukocyte glycogen 6.92 +/- 0.50 ng 10(3)-cells-1), 6 insulin-treated diabetic patients presenting with chronic pancreatitis (blood glycogen 62.2 +/- 9.3 mg l-1, leukocyte glycogen 6.69 +/- 0.70 ng 10(3)-cells-1) and 12 Type 2 insulin-treated patients (blood glycogen 53.7 +/- 4.3 mg l-1, leukocyte glycogen 7.51 +/- 0.44 ng 10(3)-cells-1). In severely ketotic patients, leukocyte counts and blood glycogen (160.8 +/- 29.6 mg l-1, p less than 0.01 vs stable diabetic patients) were increased, but the leukocytic glycogen content was not significantly affected either before or during intensive insulin therapy and rehydration. The leukocyte glycogen content was abnormally low, however, in 9 untreated Type 2 diabetic patients (5.29 +/- 0.39 ng 10(3)-cells-1, p less than 0.02 vs healthy subjects) and abnormally high (10.77 +/- 0.65 ng 10(3)-cells-1, p less than 0.005 vs healthy individuals) in 30 Type 2 patients treated by sulphonylurea, alone or in combination with insulin. No correlation was found between leukocyte glycogen and either fasting plasma glucose or HbA1c.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Sorbitol concentration in the plasma and erythrocytes of diabetic subjects.

Sorbitol content of plasma and red blood cells is increased in diabetic subjects, and it correlates with plasma glucose concentration. Rapid changes in plasma glucose concentration, either during normalization or impairment of glucose homeostasis, are paralleled by equally rapid changes in plasma or erythrocyte sorbitol content. At variance with a recent proposal, it is concluded that the measurement of sorbitol in red cells is not a reliable indicator of either long-term blood glucose levels or sorbitol accumulation in those tissues in which such an accumulation participates in the pathogenesis of degenerative complications.

Adult↗

PubMedDate not supplied

Diabetic microangiopathic hemolytic anemia: beneficial effect of an antiplatelet agent?

A 66-yr-old man with non-insulin-dependent diabetes mellitus complicated by retinopathy and nephropathy presented with shortened red cell survival associated with prominent fragmentation of erythrocytes and leading to severe hemolytic anemia. Neither abnormal carbohydrate tolerance per se nor renal failure was related to the red cell fragmentation syndrome. Also, a marked platelet hyperaggregability, which disappeared under treatment with ticlopidine, was demonstrated. Furthermore, during treatment with this potent platelet inhibitor, red cell survival normalized and all signs of hemolysis, as well as the schistocytes present in the peripheral blood smears, disappeared. Two weeks after stopping ticlopidine administration, microangiopathic hemolytic anemia relapsed. We suggest that the fragmentation hemolysis in this patient was related to diabetic microangiopathy, and that the beneficial effects of ticlopidine are related to its platelet-inhibiting activities. This case further reaffirms that antiplatelet agents may have a beneficial effect on the vascular disease of diabetes mellitus.

Aged↗

PubMedDate not supplied