Glyparamide

Emerging Theranostic Nanomaterials in Diabetes and Its Complications

Diabetes mellitus (DM) refers to a group of metabolic disorders that are characterized by hyperglycemia. Oral subcutaneously administered antidiabetic drugs such as insulin, glipalamide, and metformin can temporarily balance blood sugar levels, however, long-term administration of these therapies is associated with undesirable side effects on the kidney and liver. In addition, due to overproduction of reactive oxygen species and hyperglycemia-induced macrovascular system damage, diabetics have an increased risk of complications. Fortunately, recent advances in nanomaterials have provided new opportunities for diabetes therapy and diagnosis. This review provides a panoramic overview of the current nanomaterials for the detection of diabetic biomarkers and diabetes treatment. Apart from diabetic sensing mechanisms and antidiabetic activities, the applications of these bioengineered nanoparticles for preventing several diabetic complications are elucidated. This review provides an overall perspective in this field, including current challenges and future trends, which may be helpful in informing the development of novel nanomaterials with new functions and properties for diabetes diagnosis and therapy.

Effect of sulphonylurea derivatives, SPC-703 and tolbutamide, on insulin binding by isolated rat adipocytes

The effect of oral hypoglycaemic drugs, SPC-703 [n-(p-toluenesulphonyl)-5-methyl-2-pirazoline-1-carbonami de] and tolbutamide on insulin binding by rat adipocytes from epididymal fat pads were studied. SPC-703 and tolbutamide in concentration of 1 mM added in vitro to the suspension of adipocytes had no effect on insulin binding and kinetic parameters of insulin receptors. Daily administration of 300 mg/kg body weight of SPC-703 or tolbutamide for 10 days resulted in 48% and 34% increase of specific binding of insulin by adipocytes, respectively. From the Scatchard plot it appears that the increase of binding resulted from increased affinity of insulin receptors. These results may explain extrapancreatic action of sulphonylurea derivatives.

Sulphonylureas-induced increase in insulin binding and glucose metabolism by isolated rat adipocytes

The effects of oral hypoglycaemic drugs, SPC-703 (n-/p-toluenesulphonyl/-5-methyl-2-pirazoline-1-carbonami de) and tolbutamide on insulin binding and glucose metabolism by isolated adipocytes were studied. After 10 days of administration of both sulphonylurea derivatives, no differences were observed in insulin concentration between both experimental and the control groups of animals, despite a significant fall in blood glucose level. SPC-703 and tolbutamide in concentrations of 1 mM added in vitro to the suspension of adipocytes had no effect on insulin binding or on basal and insulin simulated glucose metabolism. Daily administration of 300 mg/kg body weight of SPC-703 or tolbutamide for 10 days resulted in 48% and 34% increase of specific binding of insulin by adipocytes, respectively. From the Scatchard plot analysis we noted that the increase of binding resulted from increased affinity of insulin receptors for hormone. Simultaneous increase in basal and insulin stimulated glucose metabolism by adipocytes, as measured by 14CO2 production and 14C incorporation into cellular lipids, was observed. The results indicate that hypoglycaemic action of sulphonylureas may be explained by increased affinity of insulin receptors and the stimulating action of these compounds on peripheral glucose metabolism.

Biotransformation of a new hypoglycemic agent, N-(p-toluenesulfonyl)-5-methyl-2-pyrazoline-1-carbonamide (SPC-703) in humans and rats

Over 60% of a dose of N-(p-toluenesulfonyl)-5-methyl-2-pyrazoline-1-carbonamide (SPC-703) given to humans or rats was excreted with urine, one third of the dose was eliminated in unchanged form. From the urine of both species two metabolites of SPC-703, M1 and M2, were isolated and their chemical structures was established. Metabolite M1 is a carboxy- and metabolite M2 a hydroxy derivative of SPC-703.

Influence of some salicylates and sulfonamides on binding by albumin of SPC-703 and tolbutamide

Bovine serum albumin has two different binding sites for sulfonylurea. The sites at high affinity can bind up to 2 moles of a new hypoglycemic sulfonylurea SPC-703 (k1=6.8.10(3) M(-1)) or tolbutamide K1=19.3.10(3) M(-1)). The sites of lower affinity can bind 4 mole of SPC-703 (K2=1.6.10(3) M(-1)) or 8 moles of tolbutamide (k2=1.3.10(3) M(-1)). Binding of SPC-703 and tolbutamide was decreased mostly in the presence of sulfadimetoxine, but this sulfonamide increased the concentration of free tolbutamide more than that of SPC-703.