Researchers at the University of Geneva (UNIGE) report they have discovered the underlying biological mechanisms responsible for insulin deficiencies in diabetic patients – research they believe could end the need for regular injections and result in new types of treatment for the condition.
Insulin is a hormone secreted by beta cells in the pancreas, and deficiencies of it plays a major role in the regulation of glucose and other energy substrates, the university explained in a statement Tuesday. Those deficiencies, which are primarily caused by type 1 or type 2 diabetes, have lethal consequences if left untreated.
However, daily insulin injections can have serious side effects. Now, in research appearing in the journal Cell Metabolism, Roberto Coppari and colleagues from the UNIGE Department of Cell Physiology and Metabolism state that they have successfully demonstrated that insulin is not necessarily essential for survival.
“By eliminating this dogma, scientists are now considering alternatives to insulin treatment, which poses many risks to patients,” the university explained. “An error in dosage may cause hypoglycemia, i.e., a decrease in the level of glucose in the blood, which can lead to a loss of consciousness. In addition, about 90 percent of patients over 55 who have been undergoing treatment for several years develop cardiovascular disease due to elevated levels of cholesterol brought on by the lipogenic properties of insulin.”
Coppari’s team conducted a series of experiments in which they administered leptin, a hormone which regulates the body’s appetite and fat reserves, to rodents who were devoid of insulin. Despite their lack of the glucose-regulating hormone, the rats were able to survive thanks to the leptin. The authors explain that using the fat-regulating hormone has two advantages over insulin: it does not provoke hypoglycemia and it has a lipolytic effect.
“Through this discovery, the path to offering an alternative to insulin treatment is emerging. Now we need to understand the mechanisms through which leptin affects glucose level, regardless of insulin level,” Coppari explained.
His team also discovered that GABAergic neurons located in the hypothalamus were the primary mediators of leptin’s glucose-level activity when insulin deficiency was present. In addition, they were able to detect that the liver, the soleus muscle, and brown adipose tissue are affected by leptin during insulin deficiency, and that all of those areas could be potential targets for future treatments.
Thanks to that discovery, the university said, “scientists now know where to look for the answer to an insulin-free diabetes treatment. Understanding the functioning and effect of leptin on the body will enable scientists to identify the areas of the body that are involved, and ultimately the molecules that will form the basis of a new treatment.”