Dataset Information

A comparison of the anti-diabetic potential of d-ribose-l-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats.

ABSTRACT: Over 18% of pregnant women are affected by diabetes mellitus (DM) and Insulin has been the commonest drug used in its treatment. There are reports of noncompliance to insulin due to trypanophobia, with suggestions for the use of oral hypoglycaemic agents (OHAs). However, the opposing views about the benefits and risk of oral hypoglycaemic agents (OHAs) warrant a continuous search for an alternative regimen. Therefore, this study is aimed at comparing the antidiabetic effects of d-ribose-l-cysteine (riboceine) with vildagliptin, glibenclamide, metformin, glipizide and insulin in diabetes in pregnancy. Forty (40) female Sprague-Dawley (SD) rats were mated with twenty (20) male SD rats. Diabetes was induced by streptozotocin and the female SD rats were divided into 8 groups of five (5) rats each. The animals were administered either of the OHAs vildagliptin, glibenclamide, metformin, glipizide and riboceine for a period of 19 gestational days. The results showed that streptozotocin (STZ) significantly (p?

SUBMITTER: Osinubi AAA

PROVIDER: S-EPMC6104459 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A comparison of the anti-diabetic potential of d-ribose-l-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats.

Osinubi Abraham A A AAA Medubi Leke Jacob LJ Akang Edidiong N EN Sodiq Lawal K LK Samuel Titilola A TA Kusemiju Taiwo T Osolu James J Madu Danladi D Fasanmade Olufemi O

Toxicology reports 20180809

Over 18% of pregnant women are affected by diabetes mellitus (DM) and Insulin has been the commonest drug used in its treatment. There are reports of noncompliance to insulin due to trypanophobia, with suggestions for the use of oral hypoglycaemic agents (OHAs). However, the opposing views about the benefits and risk of oral hypoglycaemic agents (OHAs) warrant a continuous search for an alternative regimen. Therefore, this study is aimed at comparing the antidiabetic effects of d-ribose-l-cystei ...[more]

PMID: 30140615

Similar Datasets

Project description:Diabetic kidney disease represents a considerable burden; around one-third of patients with type 2 diabetes develop chronic kidney disease. In health, the kidneys play an important role in the regulation of glucose homeostasis via glucose utilization, gluconeogenesis and glucose reabsorption. In patients with diabetes, renal glucose homeostasis is significantly altered with an increase in both gluconeogenesis and renal tubular reabsorption of glucose. Environmental factors, both metabolic (hyperglycaemia, obesity and dyslipidaemia) and haemodynamic, together with a genetic susceptibility, lead to the activation of pro-oxidative, pro-inflammatory and pro-fibrotic pathways resulting in kidney damage. Hyperfiltration and its haemodynamic-driven insult to the kidney glomeruli is an important player in proteinuria and progression of kidney disease towards end-stage renal failure. Control of glycaemia and blood pressure are the mainstays to prevent kidney damage and slow its progression. There is emerging evidence that some hypoglycaemic agents may have renoprotective effects which are independent of their glucose-lowering effects. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors may exert a renoprotective effect by a number of mechanisms including restoring the tubuloglomerular feedback mechanism and lowering glomerular hyperfiltration, reducing inflammatory and fibrotic markers induced by hyperglycaemia thus limiting renal damage. Simultaneous use of an SGLT-2 inhibitor and blockade of the renin-angiotensin-aldosterone system may be a strategy to slow progression of diabetic nephropathy more than either drug alone. The use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists may exert a renoprotective effect by reducing inflammation, fibrosis and blood pressure. Given the burden of diabetic kidney disease, any additional renoprotective benefit with hypoglycaemic therapy is to be welcomed. Large randomized controlled trials are currently underway investigating if these new anti-diabetic agents can provide renoprotection in diabetes.

Project description:Oral delivery is considered as the most preferred and yet most challenging mode of drug administration; especially a fragile and sensitive peptide like insulin that shows extremely low bioavailability through the gastro-intestinal (GIT) route. To address this problem, we have designed a novel drug delivery system (DDS) using precipitation-induced Barium (Ba) salt particles. The DDS can load insulin molecules and transport them through the GIT route. There were several in vitro simulation tests carried out to prove the efficiency of Ba salt particles as oral delivery candidates. All three Ba salt particles (BaSO4, BaSO3, and BaCO3) showed very good loading of insulin (>70% in all formulations) and a degree of resistance throughout a wide range of pHs from basic to acidic conditions when assessed by spectrophotometry. Particles and insulin-associated particles were morphologically assessed and characterized using FE-SEM and FT-IR. A set of tests were designed and carried out with mucin to predict whether the particles are potentially capable of overcoming one of the barriers for crossing intestinal epithelium. The mucin binding experiment demonstrated 60-100% of mucin adhesion to the three different particles. FT-IR identifies the characteristic peaks for mucin protein, particles, and particle-mucin complex re-confirming mucin adhesion to the particles. Finally, the effectiveness of nano-insulin was tested on streptozotocin (STZ) induced diabetic rats. A short acting human insulin analog, insulin aspart, was loaded into Ba salt particles at a dose of 100 IU/Kg prior to oral administration. Among the three formulations, insulin aspart-loaded BaSO4 and BaCO3 particles dramatically reduced the existing hyperglycemia. BaSO4 with loaded Insulin showed an onset of glucose-lowering action within 1 hr, with blood glucose level measured significantly lower compared to the 2nd and 3rd h (p < 0.05). Insulin-loaded BaCO3 particles showed a significant decrease in blood glucose level at 1-2 h, although the glucose level started to show a slight rise at 3rd h and by 4th h, it was back to baseline level. However, although BaSO3 particles with loaded insulin showed a trend of reduction in blood glucose level, the reduction was not found to be significant (p < 0.05) at any point in time. Therefore, oral formulations of insulin/BaSO4 and insulin/BaCO3 particles were observed as effective as native insulin aspart subcutaneous formulation in terms of onset and duration of action. Further investigation will be needed to reveal bioavailability and mechanism of action of this novel Nano-Insulin formulations.

Project description:Diabetes in pregnancy is a major burden with acute and long-term consequences. Its treatment requires adequate diagnosis and monitoring of therapy. Many experimental research on diabetes during pregnancy has been performed in rats. Recently, continuous blood glucose monitoring of non-pregnant diabetic rats revealed an increased circadian variability of blood glucose that made a single blood glucose measurement per day inappropriate to reflect glycemic status. Continuous blood glucose measurement has never been performed in pregnant rats. We wanted to perform continuous blood glucose monitoring in pregnant rats to decipher the influence of pregnancy on blood glucose in diabetic and normoglycemic status.We used the transgenic Tet29 diabetes rat model with an inducible knock down of the insulin receptor via RNA interference upon application of doxycycline (DOX) leading to insulin resistant type II diabetes. All Tet29 rats received a HD-XG telemetry implant (Data Sciences International, USA) that measured blood glucose and activity continuously. Rats were divided into four groups and blood glucose was monitored until end of pregnancy or the corresponding period: Tet29?+?DOX (diabetic) non-pregnant, Tet29?+?DOX (diabetic) pregnant, Tet29 (normoglycemic) non-pregnant, Tet29 (normoglycemic) pregnant.All analyzed rats displayed a circadian variation in blood glucose concentration. Circadian variability was much more pronounced in pregnant diabetic rats than in normoglycemic pregnant rats. Pregnancy ameliorated variation in blood glucose in diabetic situation. Pregnancy continuously decreased blood glucose during normoglycemic pregnancy. Diabetic rats were less active than normoglycemic rats. We performed a calculation showing that application of continuous blood glucose measurement reduces animal numbers needed to detect a given effect in experimental setting by decreasing variability and SD.Continuous blood glucose monitoring via a telemetry device in pregnant rats provides a more informative picture of the glycemic situation in comparison to single measurements. This could improve diagnosis and therapy of diabetes, decrease animal numbers within experimental settings, and add another physiological parameter (activity) to the analysis that could be helpful in testing therapeutic concepts targeting blood glucose levels and peripheral muscle function. We propose continuous glucose monitoring as a new tool for the evaluation of pregnant diabetic rats.

Dataset Information

A comparison of the anti-diabetic potential of d-ribose-l-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats.

Publications

A comparison of the anti-diabetic potential of d-ribose-l-cysteine with insulin, and oral hypoglycaemic agents on pregnant rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets