Pathophysiological Explanation of Cardiovascular Benefits of the SGLT2- Inhibitors
Author: Hristova, Mariyana G.
1 Division of Endocrinology, Medical center of Varna,
In 1986, Prof. Rita Levi-Montalcini was awarded the Nobel Prize for Physiology and Medicine for her fundamental discovery of nerve growth factor (NGF) and neurotrophins that subsequently developed into neurotrophic theory which is currently used in many fields of biomedical science. In the subsequent 20 years, a large number of scientific facts were accumulated and the neurotrophic theory has been transformed into clinical practice as the neurotrophic theory of the pathogenesis of metabolic syndrome and type 2 diabetes mellitus. By decreasing hyperglycemia through a non-insulin dependent mechanism, SGLT2- inhibitors also reduce insulin secretion; this reduces lipogenesis and visceral adipose tissue, plasma and tissue levels of adipocytokines. Then, insulin resistance reduction follows. The other component of SGLT2 inhibitory activity, namely the inhibition of sodium reabsorption takes part in the process of sympathetic tone reduction. Increased natriuresis is followed by reduced kaliuresis. Today, neurotrophins are known as mediators of many biological phenomena caused by their neurotrophic, metabotrophic, epitheliotrophic, and immunotrophic effects. Enhancing the beneficial effects of these neuro trophins can be expected, i.e. reducing appetite, increasing insulin secretion, weight reduction as well as improvement of carbohydrate and lipid metabolism. Body neuro-endocrine-immune balance is “restarted” by normalizing neurotrophins tissue and plasma levels. The balance between inflammatory and anti-inflammatory adipocytokines in adipose tissue is restored. All this leads to neuroprotective, cardio protective and vascular protective effects and to substantial cardiovascular benefits of SGLT2-inhibitors.
Key word: Type 2 diabetes, neurotrophins, SGLT2-inhibitors,cardiovascular benefits