Abstract
Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to β cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.
Highlights
IntroductionType 2 diabetes mellitus (T2DM) is one of the most prevalent chronic and noncommunicable diseases worldwide [1]
According to the International Diabetes Federation (IDF), 425 million people were affected by Type 2 Diabetes Mellitus (T2DM) in 2017, and a fairly conservative projection estimates an overall increase of 693 million cases by 2045 [2]
44% decrease in αTC1 cell proliferation was observed compared with the control group by counting the cells in the S phase. These results show that glucagon has direct trophic effects on α cells by an autocrine mechanism, and when the pancreatic α-cell number was decreased in db/db mice by a glucagon receptor antagonist, plasma glucagon levels were significantly decreased too [45]
Summary
Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic and noncommunicable diseases worldwide [1]. According to the International Diabetes Federation (IDF), 425 million people were affected by T2DM in 2017, and a fairly conservative projection estimates an overall increase of 693 million cases by 2045 [2]. T2DM is a metabolic disease where insulin resistance (IR), secondary to environmental and genetic factors, has a leading role in its pathophysiology [3,4]. The classic pathophysiological T2DM theorem states that muscle and liver IR is driven by chronic hypoxia, inflammation, and oxidative stress from dysfunctional visceral adipose tissue. In the precursor stages of T2DM, muscle and liver IR stimulates compensatory hyperinsulinemia (CHI) to maintain both fasting and post-prandial glucose levels near the normal range [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
