Objective: Previous work has demonstrated that chronic administration of the serotonin reuptake inhibitor (SSRI) fluoxetine augments counterregulatory responses to hypoglycemia in healthy humans. However, virtually no information exists regarding the effects of fluoxetine on integrated physiological counterregulatory responses during hypoglycemia in type 1 diabetes. Therefore, the specific aim of this study was to test the hypothesis that 6-week use of the SSRI fluoxetine would amplify autonomic nervous system (ANS) counterregulatory responses to hypoglycemia in individuals with type 1 diabetes.
Research Design And Methods: Eighteen type 1 diabetic patients (14 men/4 women aged 19-48 years with BMI 25 +/- 3 kg/m(2) and A1C 7.0 +/- 0.4%) participated in randomized, double-blind 2-h hyperinsulinemic (9 pmol . kg(-1) . min(-1))-hypoglycemic clamp studies before and after 6 weeks of fluoxetine administration (n = 8) or identical placebo (n = 10). Glucose kinetics was determined by 3-tritiated glucose. Muscle sympathetic nerve activity (MSNA) was determined by microneurography.
Results: Hypoglycemia (2.8 +/- 0.1 mmol/l) and insulinemia (646 +/- 52 pmol/l) were similar during all clamp studies. ANS, neuroendocrine, and metabolic counterregulatory responses remained unchanged in the placebo group. However, fluoxetine administration significantly (P < 0.05) increased key ANS (epinephrine, norepinephrine, and MSNA), metabolic (endogenous glucose production and lipolysis), and cardiovascular (systolic blood pressure) counterregulatory responses during hypoglycemia.
Conclusions: This study has demonstrated that 6-week administration of the SSRI fluoxetine can amplify ANS and metabolic counterregulatory mechanisms during moderate hypoglycemia in patients with type 1 diabetes. These data also suggest that the use of fluoxetine may be useful in increasing epinephrine responses during hypoglycemia in clinical practice.
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http://dx.doi.org/10.2337/db08-1000 | DOI Listing |
World J Diabetes
January 2025
Department of Gastroenterology, The First People's Hospital of Foshan, Foshan 528000, Guangdong Province, China.
In this article, we review the study by Jin , which examined the role of intestinal glucagon-like peptide-1 (GLP-1) in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus (T1DM). With the global rise of T1DM, there is an increased burden on society and healthcare systems. Due to insulin therapy and islet dysfunction, T1DM patients are highly vulnerable to severe hypoglycemia, a leading cause of mortality.
View Article and Find Full Text PDFFront Immunol
December 2024
Department of Dermatology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, United States.
Introduction: Cytokines and chemokines direct the inflammatory response and may serve as markers of immune dysregulation in Pemphigus vulgaris (PV), an autoimmune blistering skin disorder. Previous studies on limited numbers of patients and cytokine profiles in PV have produced equivocal results regarding the role these mediators play in disease.
Methods: In this study, we interrogated serum samples from 116 PV patients and 29 healthy controls by multiplexed bead array assays across a comprehensive set of cytokines and chemokines covering several functional categories, including IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, IL-21, IL-22, IL-23, TNFα, IFNγ, MCP-1, and Eotaxin.
World J Diabetes
December 2024
Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India.
Patients with type 1 diabetes mellitus (T1DM) experience multiple episodes of hypoglycemia, resulting in dysfunctional counter-regulatory responses with time. The recent experimental study by Jin explored the role of intestinal glucagon-like peptide-1 (GLP-1) in impaired counter-regulatory responses to hypoglycemia. They identified intestinal GLP-1 along with GLP-1 receptor (GLP-1R) as the new key players linked with impaired counter-regulatory responses to hypoglycemia in type 1 diabetic mice.
View Article and Find Full Text PDFWorld J Diabetes
December 2024
Department of Endocrinology and Metabolism, The Affiliated Hospital of Shandong Second Medical University, Weifang 261031, Shandong Province, China.
Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency and the need for exogenous insulin. A significant concern in T1D management is hypoglycemia, which is worsened by impaired counterregulatory mechanisms. Effective counterregulation involves hormones such as glucagon and adrenaline, which work to restore normal blood glucose levels.
View Article and Find Full Text PDFEndocrine
December 2024
Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden.
Purpose: We aimed to characterize the RYGB-induced changes in the dynamics of brain glucose uptake. We addressed heterogeneity between brain regions during experimental normo- and hypoglycemia and explored associations with anthropometric and metabolic outcomes of RYGB.
Methods: Analyses of regional brain glucose uptake were performed on 9 individuals with obesity and no diabetes, investigated with combined brain F-FDG-PET and fMRI during hyperinsulinemic normo- and hypoglycemic clamp, one month before and four months after RYGB.
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