**3. Molecular semaphore of beta cell in diabetes: integrating biomarkers with functional measures**

Circadian regulation of glucose homeostasis and insulin secretion is an important feature to assess whether islets are functional. Molecular clock mechanism is highly conserved among various cell types and is driven by a set of core clock genes that form interrelated transcriptional-translational complex. Thus understanding the molecular mechanism driving the inter relationship between disruption and islet functioning is crucial in context of disease prevention and transplantation.

The molecular mechanism governing this rhythmicity is based on complex program of gene expression. A number of interlocked transcriptional and posttranslational feedback loops are responsible for generation and maintenance of rhythms. It will be interesting to initiate a study to assess the basal levels of glut receptor; Ca2+, glucose kinase and Insulin expression immediately after the purification of islets are done. This will highlight the necessity to understand the molecular and physiological underpinnings responsible for the functionality of islets before the transplant. These basal levels of expression of all the molecular parameters will give the clinician an idea on functionality of islets even before it is transplanted. However after the transplant the levels should vary depending on the success of transplant surgery, circadian regulation and graft function [8–13].

Once the islets are transplanted to the donor, it is very important to assess the level of relevant molecular signatures in-vivo, which are involved in graft function or damage and these biomarkers decide the fate of the transplant. Optimizing engraftment and early survival after clinical islet transplantation is critical to long-term function.
