**5. Conclusion**

In conclusion, insulin secretion is stimulated by glucose, free fatty acids and amino acids after their breakdown in gut following ingestion. Glucose potentiates KATP channel-dependent insulin secretion. Free fatty acids result in insulin secretion from β-cells through free fatty acid receptor (FFAR)-1. Under incretin stimulation the amino acids trigger insulin secretion by binding to their cell surface receptors. Hormones like GLP-1 and estrogen stimulate insulin secretion, melatonin has both stimulatory and inhibitory effect and leptin and growth hormone have only inhibitory effects upon insulin secretion. Discussing about the various signaling pathways, mainly Wnt, G-proteins, EGFR, mTOR, SIRT1, PPARγ mediate increased insulin secretion, β-cell proliferation and improved GSIS in presence of nutrients, while in case of excessive nutrient load TLR4, MCP1, inflammasomes and Nrf2 impairs insulin secretion and conduces β-cell death. These excess of nutrients are the key players behind glucotoxicity and lipotoxicity, which ultimately lead to compensatory insulin secretion, β-cell mass expansion initially and β-cell death under chronic nutrients overload. Our major concern should be leading a healthy lifestyle, active routine, regular exercise, balanced diet and constant awareness about the incidence of type 2 diabetes, for eradication and curing of the disease to some extent.
