Abstract Insulin, a key hormone in the regulation of glucose homoeostasis, is secreted by pancreatic β‐cells in response to elevated glucose levels. Insulin is released in a biphasic manner in response to glucose metabolism in β‐cells. The first phase of insulin secretion is triggered by an increase in the ATP:ADP ratio; the second phase occurs in response to both a rise in ATP:ADP and other key metabolic signals, including a rise in the NADPH:NADP+ ratio. Experimental evidence indicates that pyruvate‐cycling pathways play an important role in the elevation of the NADPH:NADP+ ratio in response to glucose. The authors developed a kinetic model for the tricarboxylic acid cycle and pyruvate cycling pathways. The authors successfully validated the model against experimental observations and performed a sensitivity analysis to identify key regulatory interactions in the system. The model predicts that the dicarboxylate carrier and the pyruvate transporter are the most important regulators of pyruvate cycling and NADPH production. In contrast, the analysis showed that variation in the pyruvate carboxylase flux was compensated by a response in the activity of mitochondrial isocitrate dehydrogenase (ICDm) resulting in minimal effect on overall pyruvate cycling flux. The model predictions suggest starting points for further experimental investigation, as well as potential drug targets for the treatment of type 2 diabetes.

Providing quality cardiovascular disease (CVD) care in low resource setting requires understanding of priority and effective interventions. This study aimed to identify and prioritize evidence-based quality improvement strategies for CVD care in India using a modified two-round Delphi process in which, we asked 46 experts (clinicians, researchers, program implementers and policy makers) to rate 25 proven CVD care strategies grouped into: (1) patient support, (2) information communication technology (ICT) for health, (3) group problem solving, (4) training, and (5) multicomponent strategy on a scale of 1 (highest/best)—5 (lowest/worst) on priority, relative advantage, and feasibility. Subsequently, we convened an expert consensus panel of 32 members to deliberate and achieve consensus regarding the prioritized set of strategies for CVD care. The Delphi study found that group problem solving strategies achieved the best score for priority (1.80) but fared poorly on feasibility (2.88). Compared to others, multicomponent strategies were rated favorably across all domains (priority = 1.84, relative advantage = 1.94, and feasibility = 2.40). The ICT for health strategies achieved the worst scores for priority = 2.01, relative advantage = 2.31, and feasibility = 2.85. Training and patient support strategies scored moderately across all domains. The expert panel narrowed the selection of a multicomponent strategy consisting of (1) electronic health records with clinical decision-support system, (2) non-physician health worker facilitated care, (3) patient education materials, (4) text-message based reminders for healthy lifestyle, and (5) audit and feedback report for providers. Future research will evaluate the real-world feasibility and effectiveness of the multicomponent strategy in patients with CVD in a low- and middle-income country setting.