Combined Intranasal Insulin/Saxagliptin/Metformin Therapies Ameliorates the Effect of Combined Oral Contraceptives (Cos)-Induced Metabolic Syndrome (MetS) with a Major Target on Glucose Metabolism in Adult Female Wistar Rats: A Recent Study | Chapter 10 | New Horizons in Medicine and Medical Research Vol. 12

This study's goal is to assess the impact of long-term usage of combination oral contraceptives (COC; ethinyl estradiol and levonorgestrel) on metabolic syndrome indicators in adult female wistar rats, as well as any potential therapeutic treatment.

64 female Wistar rats were given either distilled water, Norethindrone, COC, Intranasal Insulin, Saxagliptin, Metformin, or INI+MET or INI+SAX in this study. After 8 weeks of COC exposure, the mice were separated into therapeutic groups. Indicators such as changes in body weight, insulin levels, inflammatory cytokines, glycated haemoglobin (Hb1Ac), and fasting blood glucose (FBG) levels were assessed. Treatment with INI+SAX and INI+MET considerably decreased FBG and Hb1Ac levels, while also significantly raising insulin levels in the INI+MET groups (p (leq) 0.05). Analysis of the serum lipid profile showed a statistically significant decrease in HDL levels, which were significantly increased in the INI+SAX group. In the INI+MET group, the decreased catalase activity shown in the COC group was reversed (p (leq) 0.05). The effects of COC therapy on the level of TNF-(alpha) were not significantly increased, while the effects of INI and INI + MET were. It has been proven that using MET, SAX, and INI together can reverse a number of MetS indices. This project will include a clinical phase to support and validate the preclinical findings.

Author(s) Details:

Saheed Olanrewaju Afolabi,

Department of Pharmacology and Therapeutics, University of Ilorin, Ilorin, Nigeria.

Joy Folahan,

Department of Pharmacology and Therapeutics, University of Ilorin, Ilorin, Nigeria.

Olalekan Agede,

Department of Pharmacology and Therapeutics, University of Ilorin, Ilorin, Nigeria.

Olufunke Olorundare,

Department of Pharmacology and Therapeutics, University of Ilorin, Ilorin, Nigeria.

Please see the link here: https://stm.bookpi.org/NHMMR-V12/article/view/7279

 Background information: The current study looked at the potential cardioprotective benefits of GLP1 and SGLT2i against diabetic cardiomyopathy (DCM) in type 2 diabetic rats, as well as the mechanisms behind them. The existence of heart failure in the absence of coronary artery disease is referred to as DCM.

 Methods: Forty-two male Sprague Dawley rats were randomized into four equal groups at random; a) DM+ GLP1, as DM group with GLP1 analogue (liraglutide) at a dose of 75 g/kg for 4 weeks, and DM+ SGLT2i: as DM group with SGLT2 inhibitor (dapagliflozin) at a dose of 1 mg/kg for 4 weeks. Serum blood glucose, HOMA-IR, insulin, and cardiac enzymes (LDH, CK-MB) were all tested at the end of the four-week treatment.

Myocardial oxidative stress markers (MDA, GSH, and CAT) as well as norepinephrine (NE), myocardial fibrosis, and the expression of caspase-3, TGF-, TNF-, and tyrosine hydroxylase (TH) in myocardial tissues were all assessed. As a result, T2DM resulted in a considerable increase in blood sugar levels. (p 0.05) serum glucose, HOMA-IR, serum CK-MB, and LDH In addition, DM resulted in severe myocardial damage and fibrosis, as well as an increase in myocardial MDA, NE, and upregulation of myocardial caspase-3, TNF, TGF, and TH, as well as a substantial drop in serum insulin, myocardial GSH, and CAT (p0.05). All examined indicators improved significantly (p 0.05) after administration of either GLP1 analog or SGLT2i. Conclusion: We found that both GLP1 and SGLT2i had cardioprotective effects against DCM in T2DM, with SGLT2i having the upper hand. This could be related to fibrosis, oxidative stress, apoptosis (caspase-3), sympathetic nerve activity, and other factors.

Author (s) Details

Prof. Dr. Abdelaziz M. Hussein
Department of Medical Physiology, Mansoura Faculty of Medicine, Mansoura, Egypt

Elsayed A. Eid
Department of Internal Medicine and Endocrinology, Delta University for Science and Technology, Gamasa, Egypt

Medhat Taha
Department of Anatomy, Mansoura Faculty of Medicine, Mansoura, Egypt.

Rami M. Elshazli
Department of Biochemistry, Faculty of Physical Therapy, Horus University-Egypt, New Damietta, Egypt.

Raouf Fekry Bedir
Department of Anatomy, Mansoura Faculty of Medicine, Mansoura, Egypt.


Lashin Saad Lashin
Department of Medical Physiology, Mansoura Faculty of Medicine, Mansoura, Egypt and Department of Medical Physiology, Horus University, Damietta, Egypt.

View Book :- https://stm.bookpi.org/HMMR-V9/article/view/1021