Wenli Liu
National Institutes of Health, USA
Title: Olfactomedin 4 negatively regulates glucose-stimulated insulin secretion through inhibition of mitochondrial complex I activity
Biography
Wenli Liu is currently a Staff Scientist at Molecular and Clinical Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, USA. He received his MD at Medical School of Qingdao University, China in 1988 and MSc at Dalian Medical University, China in 1991. After graduation, he had worked in the Department of Dermatology, the First Affiliated Hospital of Dalian Medical University for Several Years. He worked as a Research Associate at the Center for Endocrinology and Metabolism, Northwestern University Medical School, USA for 3 years. He joined National Institutes of Health in 2002, first as a Research Follow and later a Staff Scientist since 2007. His research interests include Hematology, Endocrinology, Cancer Research and Immunology. He has published 35 papers in peer-reviewed journals and 1 US patent. He first cloned and characterized the olfactomedin 4 (Olfm4) gene from human myeloid cells. He has published 12 Olfm4 related research papers which show that Olfm4 plays important roles in a variety of biological functions including innate immunity, inflammation and cancer.
Abstract
Olfactomedin 4 (Olfm4) is a member of olfactomeidn glycoprotein family, which plays important roles in innate immunity against bacterial infection, gastrointestinal inflammation and carcinogenesis. Several recent genome-wide association studies (GWAS) have linked polymorphisms in Olfm4 with childhood obesity. This prompted us to study the potential role of Olfm4 in pancreatic β-cells, which regulate glucose metabolism and energy balance. In this study, we have identified Olfm4 is expressed in pancreatic β-cells and further investigated its potential roles in glucose homeostasis and pathogenesis of type 2 diabetes using Olfm4 deficient mouse models. Compared with wild-type mouse, Olfm4 deficient mouse did not show any difference in body weight, chow and fasting glucose level and insulin level. However, the Olfm4 deficient mouse showed improved glucose tolerance and this effect was accompanied with increased serum insulin levels following high glucose challenge. In vitro, islets from Olfm4 deficient mouse secreted more insulin than those in wild-type mouse after high glucose stimulation. Mitochondrial adenosine triphosphate (ATP) production in Olfm4 deficient mouse islets was also significantly higher than wild-type mouse islets. We also investigated the effect of Olfm4 overexpression on insulin secretion in Min6 cells. Olfm4 overexpression in Min6 cells lowers basal insulin level and glucose stimulated insulin level. Accordingly, the ATP production and complex I activity in Olfm4 overexpressed Min6 cells were significantly decreased compared with control Min6 cells. Under high-fat diet conditions, glucose stimulated insulin secretion increase fold was significantly higher in Olfm4 deficient mice than in WT mice. The impaired glucose tolerance in high-fat diet-fed mice was improved by deletion of Olfm4. When Olfm4 was deleted in ob/ob mouse, the fasting glucose level in these mice was significantly lower than those in the ob/ob mice. These studies established that Olfm4 negatively regulates glucose-stimulated insulin secretion through inhibition ATP production and complex I activity. Olfm4 may become a potential therapeutic target for impaired glucose tolerance and type-2 diabetes patients.
Ngozi F Nnolum-Orji
Nelson Mandela Metropolitan University, South Africa
Title: High-fat-diet induced insulin resistance and prevention with Sutherlandia frutescens – Role of 11βHSD-1
Biography
Ngozi F Nnolum-Orji is currently completing her MSc degree in Biochemistry at Nelson Mandela Metropolitan University. Her research interest is focused on Diabetes prevention and treatment using medicinal plants, hence, has secured admission for her PhD studies on properties of identified anti-diabetic medicinal plant at the Department of Pharmacology, University of Pretoria.
Abstract
11βHSD-1 is an enzyme that converts inactive cortisone to cortisol within peripheral tissues and regulates tissue cortisol levels, thus influences glucose regulation. Literatures have implicated the activity of 11β-HSD1 involving glucocorticoid receptor (GR) and phosphoenolpyruvate carboxylkinase (PEPCK), as mediator of insulin resistance (IR) developed with consumption of high fat diet (HFD). At NMMU, a HFD on which rats developed IR within 56 days was established, while extract of Sutherlandia frutescens, a South African plant, prevented IR in rats fed HFD. We investigated the role of 11β-HSD1 in the development of observed IR and the effect of S. frutescens on the enzyme expression. Using quantitative RT-PCR, periodic (days 7, 14, 28, 56, 86) mRNA expressions of 11β-HSD1, GR and PEPCK were measured in rat liver tissues. Also, 11β-HSD1 protein expression was analysed using immunohistochemistry techniques. There was no significant change in 11β-HSD1 expression till day 56, but increased mRNA and protein levels were observed at day 86 (i.e 30 days after IR had developed). Increased mRNA levels of PEPCK was observed prior to IR in rats fed HFD, indicating increased gluconeogenesis, but did not increase in rats fed HFD and S. frutescens. mRNA levels of GR showed no pattern of GR regulation. Increased 11β-HSD1 activity is possibly a consequence of IR rather than cause, but may play a role in the development of type 2 diabetes, by further enhancing IR. Increased gluconeogenesis was induced via other mechanisms, while S. frutescens prevented increased gluconeogenesis in rats fed HFD and S. frutescens.