Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

Su, Jingqian; Luo, Yingsheng; Hu, Shan; Tang, Lu; Ouyang, Songying

doi:10.3390/ijms241713381

Cited by 18 publications

(9 citation statements)

References 180 publications

(272 reference statements)

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“…T2DM requires effective therapeutic targets [38]. The proper management of T2DM may be well achieved using combination therapy rather than monotherapy [39].…”

Section: Discussionmentioning

confidence: 99%

The Safety and Efficacy of Combining Saxagliptin and Pioglitazone Therapy in Streptozocin-Induced Diabetic Rats

Othman,

Ashour Ibrahim,

Saleh

et al. 2023

Biomedicines

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Background: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease due to insulin resistance. Oxidative stress complicates the etiology of T2DM. Saxagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, while Pioglitazone is a thiazolidinedione insulin sensitizer. This study aimed to assess the effect of Saxagliptin and Pioglitazone monotherapy and combination therapy on the biochemical and biological parameters in streptozotocin (STZ)-induced diabetic rats. Methods: The study included thirty-five male albino rats. Diabetes mellitus was induced by intraperitoneal STZ injection (35 mg/kg). For a 1-month duration, rats were divided into five groups. Glucose homeostasis traits, lipid profiles, kidney functions, liver enzymes, and oxidative stress markers were measured. Gene expression of miRNA-29a, phosphoenolpyruvate carboxykinase (PEPCK), phosphoinositide-3-kinase (PI3K), and interleukin 1 beta (IL-1β) was assessed using qRT-PCR. Results: At a 1-month treatment duration, combination therapy improves oxidative stress markers more than either drug alone. The combination therapy had significantly higher levels of SOD, catalase, and GSH and lower levels of MDA compared to the monotherapy. Additionally, the diabetic group showed a significant increase in the expression levels of miRNA-29a, PEPCK, and IL-1β and a significant decrease in PI3K compared to the normal control group. However, combination therapy of Saxagliptin and Pioglitazone was more effective than either Saxagliptin or Pioglitazone alone in reversing these results, especially for PEPCK and IL-1β. Conclusions: Our findings revealed that combining Saxagliptin and Pioglitazone improves glycemic control and genetic and epigenetic expression profiles, which play an essential regulatory role in normal metabolism.

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“…T2DM requires effective therapeutic targets [38]. The proper management of T2DM may be well achieved using combination therapy rather than monotherapy [39].…”

Section: Discussionmentioning

confidence: 99%

The Safety and Efficacy of Combining Saxagliptin and Pioglitazone Therapy in Streptozocin-Induced Diabetic Rats

Othman,

Ashour Ibrahim,

Saleh

et al. 2023

Biomedicines

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“…However, human studies are required to assess the real therapeutic value of baicalin in alleviating diabetes-related disturbances. Given that diabetes is a chronic disease, long-term treatment with anti-diabetic drugs is required [ 103 , 104 ]. The hormonal and metabolic disturbances in people with diabetes are associated with grave diabetes complications [ 105 , 106 ].…”

Section: Conclusion and Additional Remarksmentioning

confidence: 99%

The Anti-Diabetic Potential of Baicalin: Evidence from Rodent Studies

Szkudelski,

Szkudelska

2023

IJMS

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Baicalin is a biologically active flavonoid compound that benefits the organism in various pathological conditions. Rodent studies have shown that this compound effectively alleviates diabetes-related disturbances in models of type 1 and type 2 diabetes. Baicalin supplementation limited hyperglycemia and improved insulin sensitivity. The anti-diabetic effects of baicalin covered the main insulin-sensitive tissues, i.e., the skeletal muscle, the adipose tissue, and the liver. In the muscle tissue, baicalin limited lipid accumulation and improved glucose transport. Baicalin therapy was associated with diminished adipose tissue content and increased mitochondrial biogenesis. Hepatic lipid accumulation and glucose output were also decreased as a result of baicalin supplementation. The molecular mechanism of the anti-diabetic action of this compound is pleiotropic and is associated with changes in the expression/action of pivotal enzymes and signaling molecules. Baicalin positively affected, among others, the tissue insulin receptor, glucose transporter, AMP-activated protein kinase, protein kinase B, carnitine palmitoyltransferase, acetyl-CoA carboxylase, and fatty acid synthase. Moreover, this compound ameliorated diabetes-related oxidative and inflammatory stress and reduced epigenetic modifications. Importantly, baicalin supplementation at the effective doses did not induce any side effects. Results of rodent studies imply that baicalin may be tested as an anti-diabetic agent in humans.

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“…T2DM has become a heavy burden for patients all over the world, and its incidence rate is rising, accounting for more than 90% of the global diabetes cases [3] . According to the prediction of the World Health Organization, diabetes will become the seventh leading cause of death by 2030 [4] . At present, the clinical intervention for T2DM mainly depends on insulin supplementation or hypoglycemic drugs, but it cannot be eradicated [5] .…”

Section: Introductionmentioning

confidence: 99%

Study on Isoquercitrin Relieving Insulin Resistance of RNF6 Overexpressing db/db Mice

2024

FMSR

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Insulin resistance is the main pathogenesis of type 2 diabetes. Previous studies have proved that isoquercitrin, a natural flavonoid extracted from Bidens bipinnata, can alleviate insulin resistance, but its mechanism is still unknown. Ring finger protein 6 (RNF6) is related to the degradation and ubiquitination of target protein, and it is a potential target for the treatment of insulin resistance. db/db mice were constructed with RNF6 overexpression, and their body weight and fasting blood glucose levels were recorded. After isoquercitrin administration, the body weight, fasting blood glucose and fasting insulin content of mice in each group were measured, and the pancreatic tissue morphology of mice in each group was observed by HE staining. The protein expressions of RNF6, IRS1 and PIK3R1 in cells were detected by Western blot. The results showed that RNF6 overexpression mice were successfully constructed. Overexpression of RNF6 would aggravate the insulin resistance of mice and inhibit the expression of IRS1 and PIK3R1, while isoquercitrin administration could reduce the expression of RNF6, up-regulate the expression of IRS1 and PIK3R1 and relieve the insulin resistance of mice. In a word, the above results indicate that isoquercitrin can target RNF6, up-regulate the expression of IRS1 and PIK3R1 decreased by RNF6, and relieve insulin resistance in db/db mice.

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Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

Cited by 18 publications

References 180 publications

The Safety and Efficacy of Combining Saxagliptin and Pioglitazone Therapy in Streptozocin-Induced Diabetic Rats

The Safety and Efficacy of Combining Saxagliptin and Pioglitazone Therapy in Streptozocin-Induced Diabetic Rats

The Anti-Diabetic Potential of Baicalin: Evidence from Rodent Studies

Study on Isoquercitrin Relieving Insulin Resistance of RNF6 Overexpressing db/db Mice

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