Shaima Albeloushi

Dasman Diabetic Institute

Abstract Title: Global IL-6 Knockout Improves Glucose Homeostasis Without Altering Energy Intake in Mice

Biography:

Shaima Albeloushi has completed her PhD at the University of Auckland, New Zealand, and is currently pursuing her postdoctoral studies at the Dasman Diabetes Institute. With experience working with various animal models, she was appointed as Chairperson of the Animal Care and Ethics Committee at the Dasman Diabetes Institute. Currently, she is working on different projects that focus on beta cell morphology and function, glucose homeostasis, and insulin resistance.

Research Interest:

Interleukin-6 (IL-6) is a cytokine that plays a critical role in immune regulation, inflammation, and metabolic control. Chronic elevation of IL-6, commonly observed in obesity and type 2 diabetes, is associated with insulin resistance and sustained low-grade inflammation. Clarifying the role of IL-6 is of considerable importance both physiologically and clinically. We investigated the impact of global IL-6 knock-out on glucose and whole-body energy homeostasis. Male C57BL/6 wildtype mice (n=10) and IL-6 knockout (IL-6⁻/⁻) male mice (n=10) were randomly assigned to experimental groups. Glucose and insulin sensitivity were assessed using intraperitoneal-glucosetolerance-tests (IP-GTT) and intraperitoneal-insulin-tolerance-tests (IP-ITT). Whole-body metabolic parameters were evaluated using indirect calorimetry in metabolic-cages, with continuous measurements of oxygen consumption, respiratory-exchange-ratio (RER), energy expenditure, and energy intake during 20-hours of cold exposure at 4 °C. Fasting blood glucose concentrations were comparable between IL-6⁻/⁻ and C57BL/6 mice, indicating no major differences in baseline glycemia. However, IL-6⁻/⁻ mice exhibited markedly improved glucose tolerance, compared to C57BL/6 mice. During the IP-GTT, IL-6⁻/⁻ mice showed a significantly lower area-under-the-curve (AUC:411±83mmol·L⁻¹·min⁻¹) compared with C57BL/6 controls (AUC:840±98mmol·L⁻¹·min⁻¹; P=0.005), indicating enhanced glucose clearance. Metabolic cage measurements further revealed that IL-6⁻/⁻ mice had significantly higher oxygen consumption (2.4±0.03 vs. 2.2±0.1mL·min⁻¹; P=0.001) and a higher respiratory exchange ratio (1.4±0.02 vs. 1.3±0.02; P=0.001), suggesting increased metabolic activity. Despite these differences, both groups displayed similar overall energy expenditure and caloric intake during cold exposure. These findings suggest that the global deletion of IL-6 enhances glucose and energy homeostasis, indicating a complex and context-dependent role for IL-6.