Direct effects of glucagon on glucose uptake and lipolysis in human adipocytes

Pereira, Maria J.; Thombare, Ketan; Sarsenbayeva, Assel; Kamble, Prasad G.; Almby, Kristina E.; Lundqvist, Monalill; Eriksson, Jan W.

doi:10.1016/j.mce.2019.110696

Cited by 43 publications

(45 citation statements)

References 52 publications

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“…The direct stimulation of adenylyl cyclase by forskolin bypasses receptor activation which in pancreatic adipocytes is most likely non-functional given the very low expression of beta-adrenergic and the absence of glucagon receptors (Fig. 4E, F; ref (28)(29)(30)).…”

Section: Discussionmentioning

confidence: 99%

Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity

Oquendo

Siegel-Axel

Gerst

et al. 2021

American Journal of Physiology-Cell Physiology

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Obesity, especially visceral fat accumulation, increases the risk of type 2 diabetes (T2D). The purpose of this study was to investigate the impact of T2D on the pancreatic fat depot. Pancreatic fat pads from 17 partial pancreatectomized patients (PPP) were collected, pancreatic preadipocytes isolated and in vitro differentiated. Patients were grouped using HbA1c into normal glucose tolerant (NGT), prediabetic (PD) and T2D. Transcriptome profiles of preadipocytes and adipocytes were assessed by RNAseq. Insulin sensitivity was estimated by quantifying AKT phosphorylation on western blots. Lipogenic capacity was assessed with oil red O staining, lipolytic activity via fatty acid release. Secreted factors were measured using ELISA. Comparative transcriptome analysis of preadipocytes and adipocytes indicates defective upregulation of genes governing adipogenesis (NR1H3), lipogenesis (FASN, SCD, ELOVL6, FADS1) and lipolysis (LIPE) during differentiation of cells from T2D-PPP. In addition, the ratio of leptin/adiponectin mRNA was higher in T2D than in NGT-PPP. Preadipocytes and adipocytes of NGT-PPP were more insulin sensitive than T2D-PPP cells in regard to AKT phosphorylation. Triglyceride accumulation was similar in NGT and T2D adipocytes. Despite a high expression of the receptors NPR1 and NPR2 in NGT and T2D adipocytes, lipolysis was stimulated by ANP 1.74-fold in NGT cells only. This stimulation was further increased by the PDE5 inhibitor dipyridamole (3.09-fold). Dipyridamole and forskolin increased lipolysis receptor-independently 1.88-fold and 1.48-fold, respectively, solely in NGT cells. In conclusion, the metabolic status persistently affects differentiation and lipolysis of pancreatic adipocytes. These alterations could aggravate the development of T2D.

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Section: Discussionmentioning

confidence: 99%

Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity

Oquendo

Siegel-Axel

Gerst

et al. 2021

American Journal of Physiology-Cell Physiology

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“…Its function is increasing blood glucose, by promoting glycogenolysis and gluconeogenesis. Glucagon regulates insulin and sustains glucose homeostasis in human body [26]. The glucagon binds to a G Protein Coupled Receptor (GPCR) in the cell membrane.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of tears and serum for dry eye disease using ovariectomized cynomolgus monkey

Yang

Wang

et al. 2020

Preprint

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Background Ovariectomized cynomolgus monkey 30 months after surgery was selected as the research object to identify protein changes in tears and serum to provide a reference for the diagnosis and pathogenesis of dry eye in menopausal women. Methods Six cynomolgus monkey were randomly divided into an experimental group and a control group (3 in each group). The experimental group underwent bilateral ovariectomy, while the control group underwent sham surgery with their ovaries reserved. Proteomic analysis was performed by LC-MS/MS on tears and serum collected from two groups. Differentially expressed proteins were identified and were performed cluster analysis, which included gene ontology, the Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction. Results 33 differentially expressed proteins have been identified in tears and17 differentially expressed proteins have been identified in serum. Kyoto Encyclopedia of Genes and Genomes enrichment analysis in tears has discovered Glucagon signaling pathway and neurotrophin signaling pathway may play an important role in the pathogenesis of dry eye. Gene ontology enrichment analysis in serum has discovered insulin-like growth factor binding and growth factor binding in molecular function probably make effort in pathogenesis of dry eye. KEGG analysis in serum has discovered salivary secretion may be the key pathway in pathogenesis of dry eye. Conclusions Protein G7PCH4, Q2PG17 and G7PT55 in tears may be the key protein in pathogenesis of dry eyes. Protein G7P1T1, G7PUN9 and G8F302 in serum may play an important role in pathogenesis of dry eyes.

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“…Just like catecholamines, glucagon is elevated in situations of stress [ 93 ], including in severe burns. This pancreatic hormone produces hyperglycemia directly and exerts indirect actions on glucose metabolism through stimulation of lipolysis [ 94 ] and proteolysis [ 95 ]. At high concentrations, it increases both glucose uptake and lipolysis in human adipocytes [ 94 , 96 , 97 ].…”

Section: Glucose Metabolism In Burnsmentioning

confidence: 99%

Glucose Metabolism in Burns—What Happens?

Bădoiu

Miricescu

Stănescu-Spînu

et al. 2021

IJMS

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Severe burns represent an important challenge for patients and medical teams. They lead to profound metabolic alterations, trigger a systemic inflammatory response, crush the immune defense, impair the function of the heart, lungs, kidneys, liver, etc. The metabolism is shifted towards a hypermetabolic state, and this situation might persist for years after the burn, having deleterious consequences for the patient’s health. Severely burned patients lack energy substrates and react in order to produce and maintain augmented levels of glucose, which is the fuel “ready to use” by cells. In this paper, we discuss biological substances that induce a hyperglycemic response, concur to insulin resistance, and determine cell disturbance after a severe burn. We also focus on the most effective agents that provide pharmacological modulations of the changes in glucose metabolism.

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Direct effects of glucagon on glucose uptake and lipolysis in human adipocytes

Cited by 43 publications

References 52 publications

Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity

Pancreatic fat cells of humans with type 2 diabetes display reduced adipogenic and lipolytic activity

Proteomic analysis of tears and serum for dry eye disease using ovariectomized cynomolgus monkey

Glucose Metabolism in Burns—What Happens?

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