scholarly journals The Glucagon-Like Adipokinetic Hormone in Drosophila melanogaster – Biosynthesis and Secretion

2021 ◽  
Vol 12 ◽  
Author(s):  
Bryon N. Hughson
Keyword(s):  
Diabetes Mellitus ◽  
Drosophila Melanogaster ◽  
Endocrine Cells ◽  
Epigenetic Inheritance ◽  
Glucagon Secretion ◽  
Metabolic Homeostasis ◽  
Adipokinetic Hormone ◽  
Future Directions ◽  
Glucagon And Insulin

Metabolic homeostasis requires the precise regulation of circulating sugar titers. In mammals, homeostatic control of circulating sugar titers requires the coordinated secretion and systemic activities of glucagon and insulin. Metabolic homeostasis is similarly regulated in Drosophila melanogaster through the glucagon-like adipokinetic hormone (AKH) and the Drosophila insulin-like peptides (DILPs). In flies and mammals, glucagon and AKH are biosynthesized in and secreted from specialized endocrine cells. KATP channels borne on these cells respond to fluctuations in circulating glucose titers and thereby regulate glucagon secretion. The influence of glucagon in the pathogenesis of type 2 diabetes mellitus is now recognized, and a crucial mechanism that regulates glucagon secretion was reported nearly a decade ago. Ongoing efforts to develop D. melanogaster models for metabolic syndrome must build upon this seminal work. These efforts make a critical review of AKH physiology timely. This review focuses on AKH biosynthesis and the regulation of glucose-responsive AKH secretion through changes in CC cell electrical activity. Future directions for AKH research in flies are discussed, including the development of models for hyperglucagonemia and epigenetic inheritance of acquired metabolic traits. Many avenues of AKH physiology remain to be explored and thus present great potential for improving the utility of D. melanogaster in metabolic research.

Inflammatory Markers Associated With Diabetes Mellitus – Old and New Players

2020 ◽  
Vol 26 ◽  
Author(s):  
Emir Muzurović ◽  
Zoja Stanković ◽  
Zlata Kovačević ◽  
Benida Šahmanović Škrijelj ◽  
Dimitri P Mikhailidis
Keyword(s):  
Diabetes Mellitus ◽  
Inflammatory Markers ◽  
High Specificity ◽  
Future Directions ◽  
Effective Strategies ◽  
Advantages And Disadvantages ◽  
Type 2 Dm ◽  
Increased Risk ◽  
Made In

: Diabetes mellitus (DM) is a chronic and complex metabolic disorder, and also an important cause of cardiovascular (CV) diseases (CVDs). Subclinical inflammation, observed in patients with type 2 DM (T2DM), cannot be considered the sole or primary cause of T2DM in the absence of classical risk factors, but it represents an important mechanism that serves as a bridge between primary causes of T2DM and its manifestation. Progress has been made in the identification of effective strategies to prevent or delay the onset of T2DM. It is important to identify those at increased risk for DM by using specific biomarkers. Inflammatory markers correlate with insulin resistance (IR) and glycoregulation in patients with DM. Also, several inflammatory markers have been shown to be useful in assessing the risk of developing DM and its complications. However, the intertwining of pathophysiological processes and the not-quite-specificity of inflammatory markers for certain clinical entities limits their practical use. In this review we consider the advantages and disadvantages of various inflammatory biomarkers of DM that have been investigated to date as well as possible future directions. Key features of such biomarkers should be high specificity, non-invasiveness and cost-effectiveness.

scholarly journals Preserved Inhibitory Potency of GLP-1 on Glucagon Secretion in Type 2 Diabetes Mellitus

2009 ◽  
Vol 94 (12) ◽  
pp. 4679-4687 ◽  
Author(s):  
Kristine J. Hare ◽  
Filip K. Knop ◽  
Meena Asmar ◽  
Sten Madsbad ◽  
Carolyn F. Deacon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucagon Secretion ◽  
Inhibitory Potency

scholarly journals Pathways of Glucagon Secretion and Trafficking in the Pancreatic Alpha Cell: Novel Pathways, Proteins, and Targets for Hyperglucagonemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Farzad Asadi ◽  
Savita Dhanvantari
Keyword(s):  
Diabetes Mellitus ◽  
Intracellular Trafficking ◽  
Cell Biology ◽  
Glucagon Secretion ◽  
Alpha Cell ◽  
Cell Dysfunction ◽  
Patients With Diabetes ◽  
Pancreatic Alpha Cell

Patients with diabetes mellitus exhibit hyperglucagonemia, or excess glucagon secretion, which may be the underlying cause of the hyperglycemia of diabetes. Defective alpha cell secretory responses to glucose and paracrine effectors in both Type 1 and Type 2 diabetes may drive the development of hyperglucagonemia. Therefore, uncovering the mechanisms that regulate glucagon secretion from the pancreatic alpha cell is critical for developing improved treatments for diabetes. In this review, we focus on aspects of alpha cell biology for possible mechanisms for alpha cell dysfunction in diabetes: proglucagon processing, intrinsic and paracrine control of glucagon secretion, secretory granule dynamics, and alterations in intracellular trafficking. We explore possible clues gleaned from these studies in how inhibition of glucagon secretion can be targeted as a treatment for diabetes mellitus.

Pharmacotherapy for Type 2 Diabetes Mellitus: What’s Up and Coming in the Glucagon-Like Peptide-1 (GLP-1) Pipeline?

2021 ◽  
pp. 089719002110490
Author(s):  
Mary J. Elder ◽  
Emily J. Ashjian
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Glucagon Secretion ◽  
New Drugs ◽  
Beneficial Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1), an incretin hormone, is known to lower glucose levels, suppress glucagon secretion, and slow gastric emptying. These properties make GLP-1 an ideal target in treating type 2 diabetes mellitus (T2DM). There are many FDA-approved GLP-1 agonists on the market today, several of which have demonstrated benefit beyond improving glycemic control. Given the beneficial effects of GLP-1 agonists in patients with T2DM, new drugs are in development that combine the mechanism of action of GLP-1 receptor agonism with novel mechanisms and with drugs that promote GLP-1 secretion. These agents are designed to improve glycemic control and target greater body weight reduction. This article discusses new GLP-1 drugs in the pipeline for the treatment of T2DM.

scholarly journals Glucose sensing by gut endocrine cells and activation of the vagal afferent pathway is impaired in a rodent model of type 2 diabetes mellitus

2012 ◽  
Vol 302 (6) ◽  
pp. R657-R666 ◽  
Author(s):  
Jennifer Lee ◽  
Bethany P. Cummings ◽  
Elizabeth Martin ◽  
James W. Sharp ◽  
James L. Graham ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endocrine Cells ◽  
Glucose Sensing ◽  
Afferent Neurons ◽  
Cellular Activation ◽  
Vagal Afferent ◽  
Gut Endocrine Cells

Glucose in the gut lumen activates gut endocrine cells to release 5-HT, glucagon-like peptide 1/2 (GLP-1/2), and glucose-dependent insulinotropic polypeptide (GIP), which act to change gastrointestinal function and regulate postprandial plasma glucose. There is evidence that both release and action of incretin hormones is reduced in type 2 diabetes (T2D). We measured cellular activation of enteroendocrine and enterochromaffin cells, enteric neurons, and vagal afferent neurons in response to intestinal glucose in a model of type 2 diabetes mellitus, the UCD-T2DM rat. Prediabetic (PD), recent-diabetic (RD, 2 wk postonset), and 3-mo diabetic (3MD) fasted UCD-T2DM rats were given an orogastric gavage of vehicle (water, 0.5 ml /100 g body wt) or glucose (330 μmol/100 g body wt); after 6 min tissue was removed and cellular activation was determined by immunohistochemistry for phosphorylated calcium calmodulin-dependent kinase II (pCaMKII). In PD rats, pCaMKII immunoreactivity was increased in duodenal 5-HT ( P < 0.001), K ( P < 0.01) and L ( P < 0.01) cells in response to glucose; glucose-induced activation of all three cell types was significantly reduced in RD and 3MD compared with PD rats. Immunoreactivity for GLP-1, but not GIP, was significantly reduced in RD and 3MD compared with PD rats ( P < 0.01). Administration of glucose significantly increased pCaMKII in enteric and vagal afferent neurons in PD rats; glucose-induced pCaMKII immunoreactivity was attenuated in enteric and vagal afferent neurons ( P < 0.01, P < 0.001, respectively) in RD and 3MD. These data suggest that glucose sensing in enteroendocrine and enterochromaffin cells and activation of neural pathways is markedly impaired in UCD-T2DM rats.

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