Triple negative breast cancer (TNBC) is an aggressive, challenging disease to treat. It usually arises in obese women with type II diabetes. Insulin and IGF1 pathway explained partially the relationship between type II diabetes and breast cancer. Consequently, further exploration of other overlapping pathways will help better understand this relationship. We previously showed that hypoglycemia led to proteosomic degradation of VEGFR-2 in ovarian cancer cells. In this study we investigated whether VEGF/VEGFR-2 signaling pathway bridges between the two diseases. Therefore, we modeled type II diabetes complications in vitro by exposing breast cancer cell lines MDA-MB-231 parental and its two metastatic variants to the bone and brain. The former cells were exposed to physiological, hypoglycemic and hyperglycemic glucose concentrations. On the contrary of what we found in ovarian cancer, hypoglycemia did not degrade VEGFR-2 but rather its posttranslational glycosylation was depleted and reversed rapidly upon the restoration of glucose. Cyclohexamide treatment proved that VEGFR-2 was not a product of de-novo synthesis. Generally, Hypoglycemia resulted in a decrease of the cell proliferation and their ability to form colonies. MDA-MB-231BR showed a unique sensitivity to hypo/hyperglycemia in terms of morphological changes, metabolic activity, secreted VEGF, TGF-B levels and exclusively expressed Integrin-B3 which was proportionally increased with glucose concentration. This molecular profiling might give an insight of how parental and metastasized breast cancer responds to the two well-known drugs metformin and Bevacizumab and hopefully will aid to fine tune the choice of treatment plan by the oncologist depending on whether a molecule is stable or not during the progression of the disease.