Effects of cytochalasin B and D upon insulin release and pancreatic islet cell metabolism.

Cytochalasin B is known to enhance insulin release evoked by nutrient and non-nutrient secretagogues, including D-glucose, despite inhibiting D-glucose uptake and metabolism in pancreatic islets. In the present study, cytochalasin D, which failed to affect D-glucose uptake and metabolism by isolated islets, also augmented glucose-stimulated insulin release, but unexpectedly to a lesser extent than cytochalasin B. Such was not the case, however, in islets stimulated by non-glucidic nutrients such as 2-ketoisocaproate or the association of L-leucine and L-glutamine. This situation coincided with the fact that cytochalasin B inhibited more severely D-glucose metabolism in non-B, as distinct from B, islet cells and, in the former case, caused a relatively greater inhibition of hexose catabolism at 2.8 mM than at 16.7 mM D-glucose. Nevertheless, even in the presence of forskolin, cytochalasin B was more efficient than cytochalasin D in augmenting glucose-stimulated insulin secretion. Thus, although these data document that non-B islet cells are more sensitive than purified islet B cells to cytochalasin B, at least in terms of inhibition of D-glucose catabolism, such a difference and its possible consequence upon the release of glucagon and other non-insulinic hormones by non-B islet cells do not appear sufficient to account for the greater enhancing action of cytochalasin B, as distinct from cytochalasin D, upon glucose-stimulated insulin output. Likewise, the latter difference does not appear attributable to a greater efficiency of cytochalasin B, as compared to cytochalasin D, upon the mechanical events involved in nutrient-stimulated exocytosis of insulin granules. Hence, the present findings suggest a so-far-unidentified interference of cytochalasin B with the B-cell glucose-sensing device.

Insulinotropic action of amino acids at their physiological concentrations: I. Experiments in incubated islets.

In order to simulate physiological conditions, the influence of a mixture of 22 amino acids together with taurine, all tested at their normal concentration in plasma, upon insulin release, D-glucose metabolism and (45)Ca net uptake was investigated in isolated rat pancreatic islets. The amino acid mixture had little effect upon insulin release at low concentrations of D-glucose but augmented, by up to 50%, the release of insulin provoked by higher concentrations of D-glucose. The effects of glibenclamide, forskolin, theophylline and cytochalasin B upon insulin release evoked by D-glucose in the absence or presence of the amino acid mixture and the changes in insulin output evoked by the omission from the amino mixture or addition to media containing only D-glucose of selected amino acid(s), as well as the influence of the amino acid mixture upon D-glucose metabolism and (45)Ca net uptake, were considered as compatible with both the role of certain amino acids as nutrients and the accumulation of other amino acids as positively charged molecules in the islet cells.

[Determination of serum semicarbazide-sensitive amine oxidase activity in diabetic retinopathy in type-2 diabetes]. / A szérum szemikarbazid-szenzitív aminoxidáz enzim aktivitásának vizsgálata 2-es típusú cukorbetegség talaján kialakult diabeteses retinopathiában szenvedókben.

INTRODUCTION: Recent data suggest that the copper-containing semicarbazide-sensitive amine oxidase enzyme (SSAO) may play a role in vascular endothelial damage through conversion of certain endogenous monoamines, like methylamine into cytotoxic aldehydes, hydrogen peroxide and ammonia. SSAO is present in various human tissues and in the serum. Elevated SSAO activities have been reported in patients with both types of diabetes mellitus. The purpose of this study was to examine the possible association between serum SSAO activity and the different severity stages of diabetic retinopathy. PATIENTS AND METHODS: A prospective study was performed on a defined group of Type 2 diabetic patients (n = 93) compared to non-diabetic control subjects (n = 42). All participants underwent a detailed ocular examination (slit lamp, colour retinal photography, fluorescein angiography) and standard laboratory investigations. Age at diagnosis, duration of diabetes, presence of systemic hypertension, medication and BMI were recorded. Serum SSAO activity was determined by a radiometric procedure using [14C]-benzylamine as substrate. RESULTS: In the total group of Type 2 diabetic patients SSAO activity (mean +/- SD) was significantly elevated compared to non-diabetic controls (n = 93, 131.72 +/- 53.07 vs. n = 42, 89.56 +/- 26.89 pmol.mg-1 protein.hour-1, p < 0.0001). After dividing patients to four subgroups according to the severity of diabetic retinopathy, serum SSAO activity was significantly higher in patients with high-risk proliferative diabetic retinopathy (n = 16, 166.96 +/- 70.56 pmol.mg-1 protein.hour-1) compared to those without retinopathy (n = 42, 119.54 +/- 50.49 pmol.mg-1 protein.hour-1, p < 0.02). CONCLUSION: The results support the hypothesis that elevated SSAO activity may be involved in the pathogenesis of microvascular diabetic late complications, such as retinopathy. The pharmacological manipulation of SSAO activity might be an interesting new concept for prevention and treatment of diabetic retinopathy.