The role of protein tyrosine phosphatase 1B (PTP1B) in the pathogenesis of type 2 diabetes mellitus and its complications

Teimouri, Maryam; Hosseini, Hossein; Sadeghabadi, Zahra Arab; Babaei-Khorzoughi, Reyhaneh; Gorgani‐Firuzjaee, Sattar; Meshkani, Reza

doi:10.1007/s13105-021-00860-7

Cited by 38 publications

(20 citation statements)

References 169 publications

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“…Besides the adverse reactions caused by high concentrations, the possibility of unpredictable toxicity and side effects is small. In addition, 50–80% homology between catalytic sites of PTP1B and other phosphatases limits the use of selective PTP1B inhibitors ( 35 ). However, unlike other tyrosine phosphatases, the amino acid sequence composition and special three-dimensional structure of PTP1B in its enzyme active site, especially the basic amino acid residues, Arg45, Lys116 and Lys210, are similar to C215 in the enzyme active site in the spatial structure.…”

Section: Discussionmentioning

confidence: 99%

Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice

et al. 2022

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Diabetic cardiomyopathy (DCM) is a severe complication of diabetes mellitus that is characterized by aberrant myocardial structure and function and is the primary cause of heart failure and death in diabetic patients. Endothelial dysfunction plays an essential role in diabetes and is associated with an increased risk of cardiovascular events, but its role in DCM is unclear. Previously, we showed that S-nitroso-L-cysteine(CSNO), an endogenous S-nitrosothiol derived from eNOS, inhibited the activity of protein tyrosine phosphatase 1B (PTP1B), a critical negative modulator of insulin signaling. In this study, we reported that CSNO treatment induced cellular insulin-dependent and insulin-independent glucose uptake. In addition, CSNO activated insulin signaling pathway and promoted GLUT4 membrane translocation. CSNO protected cardiomyocytes against high glucose-induced injury by ameliorating excessive autophagy activation, mitochondrial impairment and oxidative stress. Furthermore, nebulized CSNO improved cardiac function and myocardial fibrosis in diabetic mice. These results suggested a potential site for endothelial modulation of insulin sensitivity and energy metabolism in the development of DCM. Data from these studies will not only help us understand the mechanisms of DCM, but also provide new therapeutic options for treatment.

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Section: Discussionmentioning

confidence: 99%

Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice

et al. 2022

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“…Because miR-34a overexpression markedly blunted the tyrosine phosphorylation of both IR and IRS proteins, we hypothesized that miR-34a could regulate the expression of tyrosine phosphatases. Protein-tyrosine phosphatases such as the transmembrane (receptor-like) leukocyte antigen related phosphatase (LAR) and the non-transmembrane tyrosine phosphatase PTP1B are key negative regulators of insulin signaling by dephosphorylating IR and or IRS proteins [ 50 ]. The expression of PTP1B is increased in adipocytes during obesity [ 51 , 52 ], and our findings suggest that an elevated miR-34a expression might contribute to this increase.…”

Section: Discussionmentioning

confidence: 99%

The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B

Cornejo

Vergoni

Angot

et al. 2022

Cells

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Metabolic stresses alter the signaling and actions of insulin in adipocytes during obesity, but the molecular links remain incompletely understood. Members of the microRNA-34 (miR-34 family play a pivotal role in stress response, and previous studies showed an upregulation of miR-34a in adipose tissue during obesity. Here, we identified miR-34a as a new mediator of adipocyte insulin resistance. We confirmed the upregulation of miR-34a in adipose tissues of obese mice, which was observed in the adipocyte fraction exclusively. Overexpression of miR-34a in 3T3-L1 adipocytes or in fat pads of lean mice markedly reduced Akt activation by insulin and the insulin-induced glucose transport. This was accompanied by a decreased expression of VAMP2, a target of miR-34a, and an increased expression of the tyrosine phosphatase PTP1B. Importantly, PTP1B silencing prevented the inhibitory effect of miR-34a on insulin signaling. Mechanistically, miR-34a decreased the NAD+ level through inhibition of Naprt and Nampt, resulting in an inhibition of Sirtuin-1, which promoted an upregulation of PTP1B. Furthermore, the mRNA expression of Nampt and Naprt was decreased in adipose tissue of obese mice. Collectively, our results identify miR-34a as a new inhibitor of insulin signaling in adipocytes, providing a potential pathway to target to fight insulin resistance.

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“…We first tested its potential glucose lowering effect in 3T3-L1 adipocytes and C2C12 myotubes. AMPK and PTP1B are the two favorite targets of anti-diabetic drug discovery [ 18 , 30 ]. We also tested whether 36M could influence AMPK and PTP1B.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…PTP1B has been found to regulate cell growth, apoptosis, differentiation, and cell movement trough dephosphorylation of the target molecules [ 30 , 61 ]. PTP1B is widely expressed in insulin sensitive tissues and in tissues that are affected by diabetes complications [ 30 , 62 , 63 ]. After insulin injection, PTP1B knock-out mice exhibited enhanced insulin sensitivity by increase in phosphorylation of the insulin receptor in liver and muscle tissues [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

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N-Octyl Caffeamide, a Caffeic Acid Amide Derivative, Prevents Progression of Diabetes and Hepatic Steatosis in High-Fat Diet Induced Obese Mice

Liu

Lee

et al. 2022

IJMS

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The underlying pathological mechanisms of diabetes are complicated and varied in diabetic patients, which may lead to the current medications often failing to maintain glycemic control in the long term. Thus, the discovery of diverse new compounds for developing medicines to treat diabetes and its complications are urgently needed. Polyphenols are metabolites of plants and have been employed in the prevention and treatment of a variety of diseases. Caffeic acid phenethyl ester (CAPE) is a category of compounds structurally similar to polyphenols. In this study, we aimed to investigate the antidiabetic activity and potential molecular mechanisms of a novel synthetic CAPE derivative N-octyl caffeamide (36M) using high-fat (HF) diet induced obese mouse models. Our results demonstrate that 36M prevented the progression of diabetes in the HF diet fed obese mice via increasing phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibiting expression of protein tyrosine phosphatase 1B (PTP1B). We also found that 36M could prevent hepatic lipid storage in the HF diet fed mice via inhibition of fatty acid synthase and lipid droplet proteins, including perilipins and Fsp27. In conclusion, 36M is a potential candidate compound that can be developed as AMPK inhibitor and PTP1B inhibitor for treating diabetes and hepatic steatosis.

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The role of protein tyrosine phosphatase 1B (PTP1B) in the pathogenesis of type 2 diabetes mellitus and its complications

Cited by 38 publications

References 169 publications

Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice

Myocardial protection of S-nitroso-L-cysteine in diabetic cardiomyopathy mice

The Stress-Responsive microRNA-34a Alters Insulin Signaling and Actions in Adipocytes through Induction of the Tyrosine Phosphatase PTP1B

N-Octyl Caffeamide, a Caffeic Acid Amide Derivative, Prevents Progression of Diabetes and Hepatic Steatosis in High-Fat Diet Induced Obese Mice

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