It is known that the loss or dysfunction of islet β cells in the pancreas results in an imbalance in blood glucose homeostasis, leading to the development of type 2 diabetes. Regulation of insulin and glucagon secretion, involved in glucose homeostasis, is achieved by direct sensing of glucose and other nutrients by these αlpha- and β islet cells.
These crucial secretions are also regulated via communication between islet cells and the sympathetic and parasympathetic nervous systems. However, it is still unclear how to assess how glucose homeostasis sensitivity to neurotransmitter signaling is maintained and adjusted in response to changing physiological conditions. Now, researchers at Lund University in Sweden have made two new discoveries with regard to the beta cells’ ability to release insulin. The team state that their findings can also provide an explanation as to why smokers have an increased risk of type 2 diabetes. The opensource study and is now published in the scientific journal Cell Reports.
Previous studies show that glucose-sensing neurons stimulate sympathetic norepinephrine release to repress insulin secretion and promote glucagon release. In contrast, parasympathetic acetylcholine signaling is critical for the pre-absorptive phase of insulin secretion. Alleles that increase the risk of type 2 diabetes have also been identified in the ADRA2A and the CHRM3 genes, further highlighting the importance of neurotransmitter signaling in glucose homeostasis. Despite this the molecular mechanisms controlling neurotransmitter signaling in islet β cells and their impact on diabetes development are only partially understood. The current study shows nicotine-sensitive receptors influence the normal release of insulin and that a specific genetic alteration affects the number of functional nicotine or nicotinic-sensitive receptors found in beta cells; a reduced number of functional receptors leads to a decrease in insulin secretion, thereby increasing the risk of developing type 2 diabetes.
The current study utilised glucose-intolerant, (muscoloaponeurotic fibrosacoma oncogene family A) MafA-deficient mouse model. Data findings show that MaFA controls autonomic nervous system autonomic nervous system-mediated insulin secretion by activating the transcription of nicotinic and adrenergic receptor genes. Results show that β-cell-specific deletion of the MafA transcription factor in a mouse model, which develops glucose intolerance, leads to a complete loss of insulin secretion in response to stimulation of the autonomic nervous system in vivo.
The lab explain that the receptors in the beta cells that stimulate the release of insulin are normally activated by the signal substance acetylcholine, however, they can also be activated by nicotine. They go on to add that, to their knowledge, never before has the importance of nicotine-sensitive receptors been shown in terms of the function of beta cells; their research indicates that people who lack these receptors are at higher risk of developing type 2 diabetes.
Data findings show that the gene MafA found in insulin-producing beta cells control the number of nicotine-sensitive receptors, and their ability to receive signals from the central nervous system. The lab state the effect that this single gene, MafA, alone has on insulin secretion was previously unknown, and nicotine receptors have never before been connected to type 2 diabetes.
The team surmise that it is known that smokers have an increased risk of developing type 2 diabetes, however, the reason why has not been firmly established. They go on to add that their data suggests it has to do with the nicotine-sensitive receptors. For the future, the researchers state that their findings increase knowledge about the connection between smoking and type 2 diabetes.
Source: Lund University
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
Michelle has been picked up as an expert writer for Informa publisher’s Clinical Trials community, as well as being listed as a blog source by the world’s leading medical journals, including the acclaimed Nature-Springer journal series.
Healthinnovations is currently indexed by the trusted Altmetric and PlumX metrics systems, respectively, as a blog source for published research globally. Healthinnovations is also featured in the world-renowned BioPortfolio, BioPortfolio.com, the life science, pharmaceutical and healthcare portal.
Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.
Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.
An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.