Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus

He, Xiaomei; Gao, Fei; Hou, Jiaojiao; Li, Tingjie; Tan, Junjun; Wang, Qianqian; Liu, Xiaoyan; Wang, Maoqi; Liu, Hui; Chen, Yuqin; Yu, Zhuoyuan; Yang, Mei

doi:10.1016/j.jbc.2021.101002

Cited by 32 publications

(21 citation statements)

References 44 publications

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“…Similarly, metformin protects rat insulinoma INS-1 cells from palmitate induced lipotoxic ER stress and apoptosis through decreasing JNK and p38MAPK phosphorylation via MAPK signalling pathways [ 117 , 118 ]. Moreover, metformin upregulates Aquaporin 7 in pancreatic islets (INS-1 cells) damaged by hyperglycaemic conditions through suppression of p38 and JNK mitogen activated protein kinase signalling to promote glycerol influx into β cells and subsequent promotion of insulin secretion [ 119 ].…”

Section: Evidence For Pharmaceutical Drug Induced Metabolic Adaptions...mentioning

confidence: 99%

Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences

et al. 2022

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Irreversible pancreatic β-cell damage may be a result of chronic exposure to supraphysiological glucose or lipid concentrations or chronic exposure to therapeutic anti-diabetic drugs. The β-cells are able to respond to blood glucose in a narrow concentration range and release insulin in response, following activation of metabolic pathways such as glycolysis and the TCA cycle. The β-cell cannot protect itself from glucose toxicity by blocking glucose uptake, but indeed relies on alternative metabolic protection mechanisms to avoid dysfunction and death. Alteration of normal metabolic pathway function occurs as a counter regulatory response to high nutrient, inflammatory factor, hormone or therapeutic drug concentrations. Metabolic reprogramming is a term widely used to describe a change in regulation of various metabolic enzymes and transporters, usually associated with cell growth and proliferation and may involve reshaping epigenetic responses, in particular the acetylation and methylation of histone proteins and DNA. Other metabolic modifications such as Malonylation, Succinylation, Hydroxybutyrylation, ADP-ribosylation, and Lactylation, may impact regulatory processes, many of which need to be investigated in detail to contribute to current advances in metabolism. By describing multiple mechanisms of metabolic adaption that are available to the β-cell across its lifespan, we hope to identify sites for metabolic reprogramming mechanisms, most of which are incompletely described or understood. Many of these mechanisms are related to prominent antioxidant responses. Here, we have attempted to describe the key β-cell metabolic adaptions and changes which are required for survival and function in various physiological, pathological and pharmacological conditions.

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Section: Evidence For Pharmaceutical Drug Induced Metabolic Adaptions...mentioning

confidence: 99%

Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences

et al. 2022

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“…Therefore, AQP7 is currently considered an important regulator of b-cell protein and islet glycerol content 3 . Recently, He et al 4 reported the relationship between metformin and pancreatic AQP7 expression for the first time in the world. They reported that metformin rescued pancreatic AQP7 expression and maintained insulin secretion in the diabetic state.…”

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confidence: 99%

“…First, He et al 4 checked the presence of pancreatic AQP7 by co-staining with insulin in diabetic rats and diabetic rats treated with metformin. Diabetic rats did not express AQP7 in the b-cell area, although it was expressed in the control normal glycemic group.…”

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confidence: 99%

“…Next, He et al 4 evaluated the effect of metformin on MAPK signaling with western blotting in pancreatic islets. The p38 and JNK pathways, but not the extracellular signal-regulated kinase (ERK) pathway, were activated in the type 2 diabetes group.…”

mentioning

confidence: 99%

“…Next, He et al 4 used INS-1 cells to confirm the time course of intracellular glycerol levels in the presence of 50 mmol/L glycerol under glucolipotoxicity conditions with and without metformin. Glycerol content was low under glucolipotoxicity conditions, but the content was increased in a metformin concentration-dependent manner at all time points.…”

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confidence: 99%

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Metformin induces insulin secretion by preserving pancreatic aquaporin 7 expression in type 2 diabetes mellitus

Kimura

Kaneto

2021

J of Diabetes Invest

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Signaling pathways and intervention for therapy of type 2 diabetes mellitus

Cao

Tian

Zhang

et al. 2023

MedComm

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Type 2 diabetes mellitus (T2DM) represents one of the fastest growing epidemic metabolic disorders worldwide and is a strong contributor for a broad range of comorbidities, including vascular, visual, neurological, kidney, and liver diseases. Moreover, recent data suggest a mutual interplay between T2DM and Corona Virus Disease 2019 (COVID‐19). T2DM is characterized by insulin resistance (IR) and pancreatic β cell dysfunction. Pioneering discoveries throughout the past few decades have established notable links between signaling pathways and T2DM pathogenesis and therapy. Importantly, a number of signaling pathways substantially control the advancement of core pathological changes in T2DM, including IR and β cell dysfunction, as well as additional pathogenic disturbances. Accordingly, an improved understanding of these signaling pathways sheds light on tractable targets and strategies for developing and repurposing critical therapies to treat T2DM and its complications. In this review, we provide a brief overview of the history of T2DM and signaling pathways, and offer a systematic update on the role and mechanism of key signaling pathways underlying the onset, development, and progression of T2DM. In this content, we also summarize current therapeutic drugs/agents associated with signaling pathways for the treatment of T2DM and its complications, and discuss some implications and directions to the future of this field.

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Metformin inhibits MAPK signaling and rescues pancreatic aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus

Abstract: inhibits MAPK signaling and rescues pancreatic Aquaporin 7 expression to induce insulin secretion in type 2 diabetes mellitus,

Cited by 32 publications

References 44 publications

Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences

Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences

Metformin induces insulin secretion by preserving pancreatic aquaporin 7 expression in type 2 diabetes mellitus

Signaling pathways and intervention for therapy of type 2 diabetes mellitus

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