9/23/2014 Life without insulin is possible, study suggests -- ScienceDaily

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September 3, 2013
Universit de Genve
Several millions of people around the world suffer from insulin
deficiencies. Insulin is a hormone, secreted by the beta cells in the
pancreas, which plays a major role in the regulation of energy
substrates such as glucose. This insufficiency, primarily caused by
diabetes (types 1 and 2), has lethal consequences if it is not treated.
As of now, only daily insulin injections allow certain patients to survive.
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everal millions of people around the world suffer from insulin
deficiencies. Insulin is a hormone, secreted by the beta cells in the
pancreas, which plays a major role in the regulation of energy
substrates such as glucose. This insufficiency, primarily caused by diabetes
(types 1 and 2), has lethal consequences if it is not treated. As of now, only
daily insulin injections allow patients to survive.
Several millions of people around the world suffer from insulin deficiencies. Insulin is a
hormone, secreted by the beta cells in the pancreas, which plays a major role in the
regulation of energy substrates such as glucose. This insufficiency, primarily caused
by diabetes (types 1 and 2), has lethal consequences if it is not treated. As of now,
only daily insulin injections allow patients to survive. This approach, however, brings
on serious side effects. Thanks to their research which was published in the journal
Cell Metabolism, the University of Geneva (UNIGE) scientists identified the underlying
mechanisms, proving that life without insulin is possible, and paving the way for new
diabetes treatments.
While life without insulin was inconceivable, a group of researchers, led by Roberto
Coppari, professor in the Department of Cell Physiology and Metabolism at UNIGE,
has just demonstrated that insulin is not vital for survival. By eliminating this dogma,
scientists are now considering alternatives to insulin treatment, which poses many
risks to patients. 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% 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.
Leptin leads to an essential discovery
Researchers from UNIGE's Faculty of Medicine conducted experiments on rodents
devoid of insulin, to which they administered leptin, a hormone that regulates the
body's fat reserves and appetite. Thanks to the leptin, all the subjects survived their
insulin deficiency. Using leptin offers two advantages: 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,'
explains Professor Coppari.
The studies were able to verify whether the neurons involved in the mediation of
leptin's anti-diabetic action in healthy mammals played a similar role in rodents
suffering from an insulin deficiency. The results showed that this was not the case. In
fact, to the scientists' surprise, GABAergic neurons located in the hypothalamus were
identified as the main mediators of leptin's action on glucose level in the context of
insulin deficiency. These neurons' influence on glucose had never been considered
substantial before.
Additionally, the researchers detected the peripheral tissues that are affected by leptin
during insulin deficiency. They consist mainly of the liver, the soleus muscle, and
brown adipose tissue, which could be directly targeted by future treatments.
Through this discovery, 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.
Story Source:
The above story is based on materials provided by Universit de Genve. Note:
Materials may be edited for content and length.
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Journal Reference:
1. Teppei Fujikawa, Eric D. Berglund, Vishal R. Patel, Giorgio Ramadori, Claudia R.
Vianna, Linh Vong, Fabrizio Thorel, Simona Chera, Pedro L. Herrera, Bradford B.
Lowell, Joel K. Elmquist, Pierre Baldi, Roberto Coppari. Leptin Engages a
Hypothalamic Neurocircuitry to Permit Survival in the Absence of Insulin. Cell
Metabolism, 2013; 18 (3): 431 DOI: 10.1016/j.cmet.2013.08.004
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