Figure 3.

Break down of insulin secretion and sensitivity in type-2 diabetes. At the physiological state glycaemic homeostasis is maintained by efficient communication between the insulin secreting organ, the pancreas, and insulin target organs (adipose tissue and liver). All tissues are populated by their respective tissue macrophages that participate in maintaining tissue homeostasis and physiological function. Insulin resistance is a breakdown of communication at insulin target tissues. At the onset of insulin resistance, macrophages accumulate in adipose tissue and pancreatic islets. Crown-like structures develop in adipose tissue with heterogeneously polarized macrophages and a decrease in adipocyte insulin sensitivity. Pancreatic islet size increases with increased β-cell number and increased macrophages. Increase in β-cell number allows compensatory insulin release to overcome insulin resistance. Increasing insulin resistance and systemic inflammation result in β-cell failure when insulin secretion no longer compensates for resistance and persistent hyperglycaemia develops. At the stage of type-2 diabetes, a complete breakdown in inter-organ communication occurs, insulin secretion drops and inflammatory macrophages permeate adipose tissue and the liver. Chronic inflammation, hyperglycaemia and dyslipidemia lead to the development of non-alcoholic steatohepatitis.