Drug therapies in type 2 diabetes: an era of personalised medicine

Chowdhury, Tahseen A; Grant, Paul

doi:10.7861/clinmedicine.16-5-441

Cited by 5 publications

(7 citation statements)

References 30 publications

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“…Of the therapeutic agents used to reduce symptoms of type 2 diabetes, metformin is the first-line treatment and works by reducing hepatic glucose production [ 96 ]. Thiazolidinediones act by increasing insulin sensitivity, while sulfonylureas and meglitinides increase insulin secretion [ 97 ]. Other medications are known to inhibit specific proteins involved in glucose metabolism, such as DPP-4, GLP-1 receptor, and SGLT2 [ 97 ].…”

Section: Discussionmentioning

confidence: 99%

“…Thiazolidinediones act by increasing insulin sensitivity, while sulfonylureas and meglitinides increase insulin secretion [ 97 ]. Other medications are known to inhibit specific proteins involved in glucose metabolism, such as DPP-4, GLP-1 receptor, and SGLT2 [ 97 ]. However, none of these drugs can cure type 2 diabetes, and one of the largest obstacles to developing a cure is our incomplete understanding of how insulin resistance and glucose intolerance develop.…”

Section: Discussionmentioning

confidence: 99%

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Emerging Roles of BRD7 in Pathophysiology

Park

Lee

2020

IJMS

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Bromodomain is a conserved structural module found in many chromatin-associated proteins. Bromodomain-containing protein 7 (BRD7) is a member of the bromodomain-containing protein family, and was discovered two decades ago as a protein that is downregulated in nasopharyngeal carcinoma. Since then, BRD7 has been implicated in a variety of cellular processes, including chromatin remodeling, transcriptional regulation, and cell cycle progression. Decreased BRD7 activity underlies the pathophysiological properties of various diseases in different organs. BRD7 plays an important role in the pathogenesis of many cancers and, more recently, its roles in the regulation of metabolism and obesity have also been highlighted. Here, we review the involvement of BRD7 in a variety of pathophysiological conditions, with a focus on glucose homeostasis, obesity, and cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Emerging Roles of BRD7 in Pathophysiology

Park

Lee

2020

IJMS

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“…Alternatively, pioglitazone may be given first line in circumstances where metformin is contraindicated. The blood glucose-lowering effects of thiazolidinedione can take time to be seen, with pioglitazone taking up to 4 months to achieve its maximal effects 61…”

Section: Targeting Insulin In the Treatment Of Type 2 Diabetes Mellitusmentioning

confidence: 99%

<p>Current perspective on the role of insulin and glucagon in the pathogenesis and treatment of type 2 diabetes mellitus</p>

Ojha¹,

Ojha²,

Mohammed³

et al. 2019

CPAA

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According to the World Health Organization, 422 million adults worldwide live with diabetes mellitus (DM), a significant portion of whom have type 2 diabetes. The discovery of insulin as a key regulator of glucose metabolism has revolutionized our understanding of DM and provided several therapeutic avenues. Most studies have so far predominantly focused on the role of insulin in type 2 diabetes. However, the balance between insulin and glucagon is essential in ensuring glucose homeostasis. In this review, we begin by evaluating the principal differences between insulin and glucagon with regard to their mechanism and control of their secretion. Next, we discuss their mode of action and effects on metabolism. We further explore how the two hormones impact the natural history of type 2 diabetes. Finally, we outline how current and emerging pharmacological agents attempt to exploit the properties of insulin and glucagon to benefit patients with type 2 diabetes.

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“…[13,14] Moreover, prolonged exposure to hyperglycemia is considered as the main diabetic complication. [15] Hence, the severity and clinical manifestations of PD in diabetes patients rely on the affected individual's level of blood glucose control. PD is the sixth major complication of T2DM.…”

Section: Introductionmentioning

confidence: 99%

1,25-dihydroxyvitamin-D3 promotes neutrophil apoptosis in periodontitis with type 2 diabetes mellitus patients via the p38/MAPK pathway

et al. 2018

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BackgroundAbnormal neutrophils are involved in many chronic endocrine diseases, including type 2 diabetes mellitus (T2DM), and in periodontitis (PD), which is a chronic inflammatory disease in which neutrophils play a vital role. The p38 mitogen-activated protein kinase (MAPK) signaling pathway participates in the apoptosis of many inflammatory cells. Additionally, 1,25-dihydroxyvitamin-D3 (1,25VitD3) as a regulator can induce responses to infection and tumor cell apoptosis. However, the effect of 1,25VitD3 in the pathogenic relationship between T2DM and PD remains unclear. The aim of this study was to assess the effect of 1,25VitD3 on neutrophil apoptosis in patients with T2DM and PD and the p38-MAPK-relevant signaling pathway mechanism in this process in vitro.MethodsNeutrophils were stained with Wright's stain, and apoptosis was detected by flow cytometry and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Apoptosis- and p38-related mRNAs and proteins were examined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting and ELISA. The internal relationships were analyzed using a linear regression equation and Pearson's correlation coefficient.ResultsThe highest rate of neutrophil apoptosis occurred in cultures treated with 10–8 mol/L 1,25VitD3 in the T2DM-PD group. The apoptosis rate in the T2DM-PD-p38 inhibitor group was higher than that in the healthy control group. Western blot, ELISA and qRT-PCR results showed that the mRNA and protein expression profiles of Caspase-3 and Bax were highly up-regulated and that Bcl-2 was down-regulated in the T2DM-PD-p38 inhibitor group. The expression levels of apoptotic mRNAs and proteins in the T2DM and T2DM-PD groups were significantly higher than those in the T2DM-p38 and T2DM-PD-p38 inhibitor groups. 1,25VitD3-induced neutrophil apoptosis and phosphorylated p38 (p-p38) expression were partially inhibited by the p38 inhibitor. Expression levels of apoptosis-related genes and p-p38 in neutrophils were positively associated with increasing concentrations of 1,25VitD3. p-p38 protein expression was positively associated with the level of serum 1,25VitD3.Conclusion1,25VitD3 could promote peripheral blood neutrophil apoptosis in patients with T2DM and PD through activation of the p38-MAPK signaling pathway in vitro.

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Drug therapies in type 2 diabetes: an era of personalised medicine

Cited by 5 publications

References 30 publications

Emerging Roles of BRD7 in Pathophysiology

Emerging Roles of BRD7 in Pathophysiology

<p>Current perspective on the role of insulin and glucagon in the pathogenesis and treatment of type 2 diabetes mellitus</p>

1,25-dihydroxyvitamin-D3 promotes neutrophil apoptosis in periodontitis with type 2 diabetes mellitus patients via the p38/MAPK pathway

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