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Role of Insulin Secretion, Clearance and Action in Metabolic Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 2567

Special Issue Editors


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Guest Editor
1. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA
2. Center for Diabetes and Endocrine Research, College of Medicine, University of Toledo, Toledo, OH 43606, USA
Interests: metabolic syndrome; cardiovascular derangement; physiology; pathophysiology; pharmacology; histology; biochemistry
Special Issues, Collections and Topics in MDPI journals

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Guest Editor

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Guest Editor
1. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701-2979, USA
2. Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701-2979, USA
Interests: diabetes; hypertension; insulin resistance; metabolism; metabolic diseases; physiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Metabolic diseases are reaching an epidemic worldwide. In addition to insulin resistance and impaired insulin action, altered insulin secretion and clearance contribute to the worsening of glucose and lipid metabolism. Upon its secretion from pancreatic beta cells, insulin is metabolized mostly by the liver (the first target organ), and subsequently, by peripheral tissues, in particular skeletal muscle. Thus, peripheral insulin concentrations are the result of a balance between insulin secretion and clearance. The mechanisms underlying insulin secretion and action have been widely explored. In contrast, mechanisms underlying insulin clearance remain poorly understood. This Special Issue focuses on presenting a comprehensive view on the regulation of insulin homeostasis with an overarching goal to highlight the current knowledge on the mechanisms as well as the physiologic impact of altered insulin secretion, clearance and action on metabolic processes.

We invite investigators to contribute either original research or review articles focusing on the variety of molecular mechanisms of altered insulin secretion, clearance and action, and their impact on insulin resistance and the pathogenesis of cardiometabolic diseases that include, but are not limited to, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD/NASH), atherosclerosis, hypertension in animal models and in subjects with different degrees of glucose intolerance.  Special attention will be given to the effect of dietary or pharmacological interventions on insulin metabolism. Articles should also discuss how these mechanisms cause or contribute to the progression to type 2 diabetes and associated metabolic diseases, and how they are modulated by race, sex and environmental factors.

Dr. Hilda E. Ghadieh
Prof. Dr. Amalia Gastaldelli
Prof. Dr. Sonia Michael Najjar
Guest Editors

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Keywords

  • insulin secretion
  • insulin resistance
  • insulin clearance
  • insulin endocytosis and degradation
  • insulin signaling and metabolism
  • mechanisms of altered insulin clearance
  • hepatic vs. peripheral insulin extraction
  • insulin uptake in endothelial cells and extrahepatic extraction
  • racial disparity in insulin clearance
  • environmental factors and insulin metabolism
  • diet and insulin metabolism
  • insulin metabolism and cardiometabolic disease
  • changes in insulin clearance during pharmacological treatment
  • weight gain/loss and changes in insulin secretion, clearance and action

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Published Papers (2 papers)

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Research

20 pages, 3181 KiB  
Article
Comparative Analysis of Orthosteric and Allosteric GLP-1R Agonists’ Effects on Insulin Secretion from Healthy, Diabetic, and Recovered INS-1E Pancreatic Beta Cells
by Joshua Reed, Victoria Higginbotham, Stephen Bain and Venkateswarlu Kanamarlapudi
Int. J. Mol. Sci. 2024, 25(12), 6331; https://doi.org/10.3390/ijms25126331 - 7 Jun 2024
Cited by 1 | Viewed by 803
Abstract
Despite the availability of different treatments for type 2 diabetes (T2D), post-diagnosis complications remain prevalent; therefore, more effective treatments are desired. Glucagon-like peptide (GLP)-1-based drugs are currently used for T2D treatment. They act as orthosteric agonists for the GLP-1 receptor (GLP-1R). In this [...] Read more.
Despite the availability of different treatments for type 2 diabetes (T2D), post-diagnosis complications remain prevalent; therefore, more effective treatments are desired. Glucagon-like peptide (GLP)-1-based drugs are currently used for T2D treatment. They act as orthosteric agonists for the GLP-1 receptor (GLP-1R). In this study, we analyzed in vitro how the GLP-1R orthosteric and allosteric agonists augment glucose-stimulated insulin secretion (GSIS) and intracellular cAMP production (GSICP) in INS-1E pancreatic beta cells under healthy, diabetic, and recovered states. The findings from this study suggest that allosteric agonists have a longer duration of action than orthosteric agonists. They also suggest that the GLP-1R agonists do not deplete intracellular insulin, indicating they can be a sustainable and safe treatment option for T2D. Importantly, this study demonstrates that the GLP-1R agonists variably augment GSIS through GSICP in healthy, diabetic, and recovered INS-1E cells. Furthermore, we find that INS-1E cells respond differentially to the GLP-1R agonists depending on both glucose concentration during and before treatment and/or whether the cells have been previously exposed to these drugs. In conclusion, the findings described in this manuscript will be useful in determining in vitro how pancreatic beta cells respond to T2D drug treatments in healthy, diabetic, and recovered states. Full article
(This article belongs to the Special Issue Role of Insulin Secretion, Clearance and Action in Metabolic Diseases)
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16 pages, 5604 KiB  
Article
Maternal Vitamin D Deficiency Impairs the Development of β Cells in Offspring Rats in a Sex-Dependent Manner
by Aline Z. Schavinski, Natany G. Reis, Henrique J. N. Morgan, Ana Paula Assis, Matheus L. Moro, Rafael R. Valentim, Ana Carolina Seni-Silva, Ester S. Ramos, Isis C. Kettelhut and Luiz C. C. Navegantes
Int. J. Mol. Sci. 2024, 25(8), 4136; https://doi.org/10.3390/ijms25084136 - 9 Apr 2024
Cited by 1 | Viewed by 1109
Abstract
Recent studies have shown that maternal vitamin D deficiency (VDD) causes long-term metabolic changes in offspring. However, little is known about the impact of maternal VDD on offspring endocrine pancreas development and insulin secretion in the adult life of male and female animals. [...] Read more.
Recent studies have shown that maternal vitamin D deficiency (VDD) causes long-term metabolic changes in offspring. However, little is known about the impact of maternal VDD on offspring endocrine pancreas development and insulin secretion in the adult life of male and female animals. Female rats (Wistar Hannover) were fed either control (1000 IU Vitamin D3/kg), VDD (0 IU Vitamin D3/kg), or a Ca2+-enriched VDD diet (0 IU Vitamin D3/kg + Ca2+ and P/kg) for 6 weeks and during gestation and lactation. At weaning, VDD status was confirmed based on low serum calcidiol levels in dams and pups. Next, male and female offspring were randomly separated and fed a standard diet for up to 90 days. At this age, serum calcidiol levels were restored to normal levels in all groups, but serum insulin levels were decreased in VDD males without affecting glucagon levels, glycemia, or glucose tolerance. Islets isolated from VDD males showed lower insulin secretion in response to different glucose concentrations, but this effect was not observed in VDD females. Furthermore, VDD males, but not females, showed a smaller total pancreatic islet area and lower β cell mass, an effect that was accompanied by reduced gene expression of Ins1, Ins2, Pdx1, and SLC2A2. The decrease in Pdx1 expression was not related to the methylation profile of the promoter region of this gene. Most of these effects were observed in the male VDD+Ca2+ group, indicating that the effects were not due to alterations in Ca2+ metabolism. These data show that maternal VDD selectively impairs the morphology and function of β cells in adult male offspring rats and that female offspring are fully protected from these deleterious effects. Full article
(This article belongs to the Special Issue Role of Insulin Secretion, Clearance and Action in Metabolic Diseases)
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