Lecturer Grade I, Biochemistry Department, Osun State University, Osogbo, Nigeria


The work is to screen promising compounds from plant seeds for antidiabetic/wound healing efficacies

Diabetes is a non-communicable, lifestyle disease that arise from the inability of the body to produce or use insulin, the hormone that regulates blood sugar levels. The presence of high levels of blood sugar has been found to lead to several other complications including inability of the body to repair wound as well as damage to the eye, kidney, heart and liver. My research focuses on finding natural peptides and other bioactive compounds which are able to influence how the body uses and stores sugar. These compounds should be able to regulate the functions of certain receptors and enzymes that are involved in the metabolism of sugar, regulate craving for high fat or high energy foods, and possibly be able to enhance the functions of body antioxidants towards protecting the cells from injury arising from oxidation and lipid peroxidation. This way cellular integrity can be protected for healthy living.


Reduction of endoplasmic reticulum- mitochondria interactions in beta cells from patients with type 2 diabetes.

Abstract: Type 2 diabetes develops when beta cells are not able to fulfill insulin needs. The role of the endoplasmic reticulum-mitochondria junction in coordinating the functions of these two organelles throughout the natural history of type 2 diabetes is determinant and may explain the alterations of insulin biosynthesis. Our goal was to study endoplasmic reticulum and mitochondrial interactions in human beta cells from organ donors with type 2 diabetes. Pancreas samples were obtained via the network for pancreatic organ donors with diabetes (nPOD) based on disease status with 12 subjects with type 2 diabetes and 9 non-diabetic controls. We examined pancreatic specimens by immunofluorescence, in situ hybridization and in situ proximity ligation assay and compared the results to an in vitro model of beta-cell dysfunction. Expression of proteins that enable tethering and exchanges between endoplasmic reticulum (ER) and mitochondria and quantification of interconnection through mitochondria associated membranes (MAM) was investigated. In beta cells from type 2 diabetic cases as compared to controls, there was a significant increase in reticular expression of inositol triphosphate receptor-2 (IP3R2) both at the protein and mRNA levels, no difference in mitochondrial transit peptide receptor TOM20 and mitofusin-2 expressions, and a decrease in the expression of voltage-dependent anion channel-1 (VDAC-1). The number of IP3R2-VDAC-1 complexes identified by in situ proximity ligation assay was significantly lower in diabetic islets and in beta cells of diabetics as compared to controls. Treatment of Min6-B1 cells with palmitate altered glucose-stimulated insulin secretion, increased ER stress and significantly reduced ER-mitochondrial interactions. We can conclude that specific changes in reticular and mitochondrial beta cell proteins characterize human type 2 diabetes with reduction in organelle interactions. This finding opens new targets of intervention.

Pub.: 26 Jul '17, Pinned: 22 Sep '17

A synthetic cationic antimicrobial peptide inhibits inflammatory response and the NLRP3 inflammasome by neutralizing LPS and ATP.

Abstract: Antimicrobial peptides (AMPs) are one of the most important defense mechanisms against bacterial infections in insects, plants, non-mammalian vertebrates, and mammals. In the present study, a class of synthetic AMPs was evaluated for anti-inflammatory activity. One cationic AMP, GW-A2, demonstrated the ability to inhibit the expression levels of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-activated macrophages. GW-A2 reduced LPS-induced increases in the phosphorylation of mitogen-activated protein kinase and protein kinase C-α/δ and the activation of NF-κB. GW-A2 also inhibited NLRP3 inflammasome activation induced by LPS and ATP. Furthermore, in the mice injected with LPS, GW-A2 reduced (1) the concentration of IL-1β, IL-6 and TNF-α in the serum; (2) the concentration of TNF-α in the peritoneal lavage; (3) the expression levels of iNOS, COX-2 and NLRP3 in the liver and lung; (4) the infiltration of polymorphonuclear neutrophils in the liver and lung. The underlying mechanisms for the anti-inflammatory activity of GW-A2 were found to be partially due to LPS and ATP neutralization. These results provide insights into how GW-A2 inhibits inflammation and the NLRP3 inflammasome and provide a foundation for the design of rational therapeutics for inflammation-related diseases.

Pub.: 28 Jul '17, Pinned: 22 Sep '17

Modified human glucagon-like peptide-1 (GLP-1) produced in E. coli has a long-acting therapeutic effect in type 2 diabetic mice.

Abstract: Glucagon-like peptide 1 (GLP-1) is a very potent insulinotropic hormone secreted into the blood stream after eating. Thus, it has potential to be used in therapeutic treatment of diabetes. The half-life of GLP-1, however, is very short due to its rapid cleavage by dipeptidyl peptidase IV (DPP-IV). This presents a great challenge if it is to be used as a therapeutic drug. GLP-1, like many other small peptides, is commonly produced through chemical synthesis, but is limited by cost and product quantity. In order to overcome these problems, a sequence encoding a six codon-optimized tandem repeats of modified GLP-1 was constructed and expressed in the E. coli to produce a protease-resistant protein, 6×mGLP-1. The purified recombinant 6×mGLP-1, with a yield of approximately 20 mg/L, could be digested with trypsin to obtain single peptides. The single mGLP-1 peptides significantly stimulated the proliferation of a mouse pancreatic β cell line, MIN6. The recombinant peptide also greatly improved the oral glucose tolerance test of mice, exerted a positive glucoregulatory effect, and most notably had a glucose lowering effect for as long as 16.7 hours in mice altered to create a type 2 diabetic condition and exerted a positive glucoregulatory effect in db/db mice. These results indicate that recombinant 6×mGLP-1 has great potential to be used as an effective and cost-efficient drug for the treatment of type 2 diabetes.

Pub.: 28 Jul '17, Pinned: 22 Sep '17

DPP4 gene variation affects GLP-1 secretion, insulin secretion, and glucose tolerance in humans with high body adiposity.

Abstract: Dipeptidyl-peptidase 4 (DPP-4) cleaves and inactivates the insulinotropic hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide, collectively termed incretins. DPP-4 inhibitors entered clinical practice as approved therapeutics for type-2 diabetes in 2006. However, inter-individual variance in the responsiveness to DPP-4 inhibitors was reported. Thus, we asked whether genetic variation in the DPP4 gene affects incretin levels, insulin secretion, and glucose tolerance in participants of the TÜbingen Family study for type-2 diabetes (TÜF).Fourteen common (minor allele frequencies ≥0.05) DPP4 tagging single nucleotide polymorphisms (SNPs) were genotyped in 1,976 non-diabetic TÜF participants characterized by oral glucose tolerance tests and bioimpedance measurements. In a subgroup of 168 subjects, plasma incretin levels were determined.We identified a variant, i.e., SNP rs6741949, in intron 2 of the DPP4 gene that, after correction for multiple comparisons and appropriate adjustment, revealed a significant genotype-body fat interaction effect on glucose-stimulated plasma GLP-1 levels (p = 0.0021). Notably, no genotype-BMI interaction effects were detected (p = 0.8). After stratification for body fat content, the SNP negatively affected glucose-stimulated GLP-1 levels (p = 0.0229), insulin secretion (p = 0.0061), and glucose tolerance (p = 0.0208) in subjects with high body fat content only.A common variant, i.e., SNP rs6741949, in the DPP4 gene interacts with body adiposity and negatively affects glucose-stimulated GLP-1 levels, insulin secretion, and glucose tolerance. Whether this SNP underlies the reported inter-individual variance in responsiveness to DPP-4 inhibitors, at least in subjects with high body fat content, remains to be shown.

Pub.: 28 Jul '17, Pinned: 22 Sep '17

The impact of the quality of care and other factors on progression of chronic kidney disease in Thai patients with Type 2 Diabetes Mellitus: A nationwide cohort study.

Abstract: The present study investigates the impact of quality of care (QoC) and other factors on chronic kidney disease (CKD) stage progression among Type 2 Diabetes Mellitus (T2DM) patients.This study employed a retrospective cohort from a nationwide Diabetes and Hypertension study involving 595 Thai hospitals. T2DM patients who were observed at least 2 times in the 3 years follow-up (between 2011-2013) were included in our study. Ordinal logistic mixed effect regression modeling was used to investigate the association between the QoC and other factors with CKD stage progression.After adjusting for covariates, we found that the achievement of the HbA1c clinical targets (≤7%) was the only QoC indicator protective against the CKD stage progression (adjusted OR = 0.76; 95%CI = 0.59-0.98; p<0.05). In terms of other covariates, age, occupation, type of health insurance, region of residence, HDL-C, triglyceride, hypertension and insulin sensitizer were also strongly associated with CKD stage progression.This cohort study demonstrates the achievement of the HbA1c clinical target (≤7%) is the only QoC indicator protective against progression of CKD stage. Neither of the other clinical targets (BP and LDL-C) nor any process of care targets could be shown to be associated with CKD stage progression. Therefore, close monitoring of blood sugar control is important to slow CKD progression, but long-term prospective cohorts are needed to gain better insights into the impact of QoC indicators on CKD progression.

Pub.: 29 Jul '17, Pinned: 22 Sep '17

Photoreceptor cells produce inflammatory products that contribute to retinal vascular permeability in a mouse model of diabetes.

Abstract: Recent studies suggest that photoreceptor cells produce mediators or products that contribute to retinal capillary damage in diabetes. The purpose of this study was to determine if photoreceptor cells release soluble factors that contribute to retinal vascular permeability in diabetes.To assess retinal vascular leakage, a streptozotocin-induced mouse model of diabetes, with hyperglycaemia for 8 months, and age-matched control mice, were injected with FITC-BSA. Fluorescence microscopy was used to detect leakage of FITC-BSA from the retinal vasculature into the neural retina. Ex vivo and in vitro experiments were performed to determine if photoreceptor cells released products that directly increased retinal endothelial cell permeability or cell death. Effects of products released by photoreceptors on tight junction and cell adhesion proteins were assessed by quantitative reverse transcription PCR (qRT-PCR). Inflammatory products released by photoreceptors into media were measured using protein arrays.Eight months duration of diabetes increased retinal vascular permeability in wild-type mice, but this defect was inhibited in opsin-deficient diabetic mice in which photoreceptor cells had degenerated earlier. Photoreceptor cells from diabetic wild-type mice released inflammatory products (e.g. IL-1α, IL-1β, IL-6, IL-12, chemokine C-X-C motif ligand 1 [CXCL1], monocyte chemoattractant protein 1 [MCP-1], CXCL12a, I-309, chemokine ligand 25 [CCL25] and TNF-α), which directly contributed to increased retinal endothelial cell permeability, at least in part via changes in claudin (tight junction) mRNA. Products released from photoreceptor cells from diabetic mice or under diabetes-like conditions did not directly kill retinal endothelial cells in vitro.Photoreceptor cells can produce inflammatory products that contribute to retinal vascular permeability in mouse models of diabetes.

Pub.: 30 Jul '17, Pinned: 22 Sep '17