Obesity is associated with reduced insulin sensitivity, a major factor that leads development of Type 2 diabetes. Over-nutrition induces drastic changes in the cellular metabolism that affects normal function of endoplasmic-reticulum (ER) and mitochondria which exacerbate the cellular response to insulin. Although, ER and mitochondria have their own distinct roles in regulating cellular homeostasis but these organelles also physically interact with one another to exchange lipids, calcium and other metabolites to maintain cellular bioenergetics. This juxtaposition between ER and mitochondrial is termed as Mitochondria associated ER membrane (MAM). ER calcium channel IP3R1 (Inositol 1,4,5-triphosphate receptor 1), chaperone protein GRP75 (glucose-regulated protein 75) and mitochondrial outer membrane ion channel VDAC1 (voltage dependent anion channel 1) form a macromolecular complex to mobilize calcium from ER to mitochondria at MAM interface. This macromolecular complex plays a pivotal role in regulating mitochondrial calcium levels. Previous report showed that calcium accumulation in mitochondria due to abnormal induction of MAM formation in hepatic tissue induced insulin resistance in diet induced obese (DIO) and genetically obese mice whereas suppression of MAM formation or knocking down MAM component IP3R1 improved hepatic insulin sensitivity.