PMID- 35739183 OWN - NLM STAT- MEDLINE DCOM- 20220627 LR - 20220829 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 12 IP - 1 DP - 2022 Jun 23 TI - Terminalia catappa aqueous leaf extract reverses insulin resistance, improves glucose transport and activates PI3K/AKT signalling in high fat/streptozotocin-induced diabetic rats. PG - 10711 LID - 10.1038/s41598-022-15114-9 [doi] LID - 10711 AB - Rising prevalence of type 2 diabetes mellitus (T2DM) in sub-Saharan Africa has necessitated surveys of antidiabetic medicinal plants. This study assessed the antidiabetic mechanism of Terminalia catappa aqueous leaf extract (TCA) in high fat/low dose streptozotocin-induced type 2 diabetic rats. T2DM was induced by a combination of high-fat diet and low dose STZ (30 mg/kg bw) and the animals were administered with TCA (400 and 800 mg/kg bw) orally daily for 28 days. Biochemical parameters and indices for diabetes including renal function tests and pancreatic histology were evaluated. Relative expression of hepatic insulin resistance, signalling and glucose transport genes were also assessed. Induction of T2DM resulted in significant (p < 0.05) weight loss, dysregulated glucose level and clearance, electrolyte imbalance and disrupted diabetic biochemical parameters. Diabetes onset also perturbed beta-cell function and insulin resistance indices, damaged pancreas microanatomy, while disrupting the expression of insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and glucose transporter isoform 4 (GLUT-4) mRNA. Oral treatment of diabetic animals with TCA significantly (p < 0.05) ameliorated alterations due to T2DM induction in a manner comparable with glibenclamide. These results suggest TCA exerts its antidiabetic action by reversing insulin resistance, improving glucose transport and activating PI3K/AKT signalling. CI - (c) 2022. The Author(s). FAU - Iheagwam, Franklyn Nonso AU - Iheagwam FN AD - Department of Biochemistry, Covenant University, P.M.B. 1023, Ota, Ogun State, Nigeria. franklyn.iheagwam@covenantuniversity.edu.ng. AD - Covenant University Public Health and Wellbeing Research Cluster (CUPHWERC), Covenant University, P.M.B. 1023, Ota, Ogun State, Nigeria. franklyn.iheagwam@covenantuniversity.edu.ng. FAU - Iheagwam, Olawumi Toyin AU - Iheagwam OT AD - Geniebook Associates, Ikeja, Lagos State, Nigeria. FAU - Onuoha, Michael Kemjika AU - Onuoha MK AD - Covenant University Public Health and Wellbeing Research Cluster (CUPHWERC), Covenant University, P.M.B. 1023, Ota, Ogun State, Nigeria. AD - Covenant University Health Centre, Covenant University, P.M.B. 1023, Ota, Ogun State, Nigeria. FAU - Ogunlana, Olubanke Olujoke AU - Ogunlana OO AD - Department of Biochemistry, Covenant University, P.M.B. 1023, Ota, Ogun State, Nigeria. AD - Covenant University Public Health and Wellbeing Research Cluster (CUPHWERC), Covenant University, P.M.B. 1023, Ota, Ogun State, Nigeria. FAU - Chinedu, Shalom Nwodo AU - Chinedu SN AD - Department of Biochemistry, Covenant University, P.M.B. 1023, Ota, Ogun State, Nigeria. AD - Covenant University Public Health and Wellbeing Research Cluster (CUPHWERC), Covenant University, P.M.B. 1023, Ota, Ogun State, Nigeria. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220623 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Plant Extracts) RN - 5W494URQ81 (Streptozocin) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - *Diabetes Mellitus, Experimental/drug therapy/metabolism MH - *Diabetes Mellitus, Type 2/chemically induced/drug therapy/metabolism MH - Glucose/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Insulin/metabolism MH - *Insulin Resistance MH - Phosphatidylinositol 3-Kinases/metabolism MH - *Plant Extracts/therapeutic use MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Streptozocin MH - *Terminalia/chemistry PMC - PMC9226017 COIS- The authors declare no competing interests. EDAT- 2022/06/24 06:00 MHDA- 2022/06/28 06:00 PMCR- 2022/06/23 CRDT- 2022/06/23 23:20 PHST- 2022/03/23 00:00 [received] PHST- 2022/06/17 00:00 [accepted] PHST- 2022/06/23 23:20 [entrez] PHST- 2022/06/24 06:00 [pubmed] PHST- 2022/06/28 06:00 [medline] PHST- 2022/06/23 00:00 [pmc-release] AID - 10.1038/s41598-022-15114-9 [pii] AID - 15114 [pii] AID - 10.1038/s41598-022-15114-9 [doi] PST - epublish SO - Sci Rep. 2022 Jun 23;12(1):10711. doi: 10.1038/s41598-022-15114-9.