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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 11763

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Prof. Dr. Naotake Hashimoto

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Department of Diabetes, Endocrine and Metabolic Diseases, Tokyo Women's Medical University Yachiyo Medical Center, Chiba 276-8524, Japan
Interests: cancer; diabetes; molecular mechanisms; insulin resistance; hyperglycemia; oxidative stress; growth factors
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Dear Colleagues,

Diabetes is one of the most prevalent chronic diseases, affecting about 463 million people worldwide in 2019 (8.8% of the adult population), with type 2 diabetes making up about 90% of cases. Regardless of the types of diabetes, its complications involve microvascular, macrovascular, and neuropathic issues. The treatment of diabetes, particularly type 2 diabetes, is a growing field. Metformin, which is produced from French lilac, is an oral biguanide and has been prescribed to over 120 million patients with diabetes or polycystic ovary syndrome all over the world. Molecules such as flavones, isoflavone, and chalcones have shown promising activity as inhibitors against drug targets. Many new hypoglycemic drugs have been widely used in the clinic, such as dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These drugs have significant hypoglycemic effect and low risk of hypoglycemia, with cardio- and renoprotective effect. This Special Issue focuses on high-quality research papers that address novel drug development in every type of diabetes, and welcomes papers about drug delivery systems or other kinds of molecular studies on this disorder

Prof. Dr. Naotake Hashimoto
Guest Editor

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Keywords

diabetes
drug therapy
metformin
cellular function
glycemic control
cardiovascular complications

Published Papers (6 papers)

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Research

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15 pages, 3857 KiB

Open AccessArticle

TGF-β1 Signaling Impairs Metformin Action on Glycemic Control

by Quan Pan, Weiqi Ai and Shaodong Guo

Int. J. Mol. Sci. 2024, 25(4), 2424; https://doi.org/10.3390/ijms25042424 - 19 Feb 2024

Viewed by 740

Abstract

Hyperglycemia is a hallmark of type 2 diabetes (T2D). Metformin, the first-line drug used to treat T2D, maintains blood glucose within a normal range by suppressing hepatic glucose production (HGP). However, resistance to metformin treatment is developed in most T2D patients over time. Transforming growth factor beta 1 (TGF-β1) levels are elevated both in the liver and serum of T2D humans and mice. Here, we found that TGF-β1 treatment impairs metformin action on suppressing HGP via inhibiting AMPK phosphorylation at Threonine 172 (T172). Hepatic TGF-β1 deficiency improves metformin action on glycemic control in high fat diet (HFD)-induced obese mice. In our hepatic insulin resistant mouse model (hepatic insulin receptor substrate 1 (IRS1) and IRS2 double knockout (DKO)), metformin action on glycemic control was impaired, which is largely improved by further deletion of hepatic TGF-β1 (TKObeta1) or hepatic Foxo1 (TKOfoxo1). Moreover, blockade of TGF-β1 signaling by chemical inhibitor of TGF-β1 type I receptor LY2157299 improves to metformin sensitivity in mice. Taken together, our current study suggests that hepatic TGF-β1 signaling impairs metformin action on glycemic control, and suppression of TGF-β1 signaling could serve as part of combination therapy with metformin for T2D treatment. Full article

(This article belongs to the Special Issue Drug Therapies for Diabetes)

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16 pages, 975 KiB

Open AccessArticle

Fermentation of Murta (Ugni molinae) Juice: Effect on Antioxidant Activity and Control of Enzymes Associated with Glucose Assimilation

by Natalia Escobar-Beiza, José R. Pérez-Correa and Wendy Franco

Int. J. Mol. Sci. 2023, 24(20), 15197; https://doi.org/10.3390/ijms242015197 - 15 Oct 2023

Viewed by 986

Abstract

Berries are rich in bioactive compounds, including antioxidants and especially polyphenols, known inhibitors of starch metabolism enzymes. Lactic acid fermentation of fruits has received considerable attention due to its ability to enhance bioactivity. This study investigated the effect of fermentation with L. mesenteroides of juice from the Chilean berry murta on antioxidant activity, release of polyphenols, and inhibitory activity against α-amylase and α-glucosidase enzymes. Three types of juices (natural fruit, freeze-dried, and commercial) were fermented. Total polyphenol content (Folin–Ciocalteu), antioxidant activity (DPPH and ORAC), and the ability to inhibit α-amylase and α-glucosidase enzymes were determined. Fermented murta juices exhibited increased antioxidant activity, as evidenced by higher levels of polyphenols released during fermentation. Inhibition of α-glucosidase was observed in the three fermented juices, although no inhibition of α-amylase was observed; the juice from freeze-dried murta stood out. These findings highlight the potential health benefits of fermented murta juice, particularly its antioxidant properties and the ability to modulate sugar assimilation by inhibiting α-glucosidase. Full article

(This article belongs to the Special Issue Drug Therapies for Diabetes)

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Review

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16 pages, 2406 KiB

Open AccessReview

Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity

by Stjepan Eržen, Gašper Tonin, Dubravka Jurišić Eržen and Jasna Klen

Int. J. Mol. Sci. 2024, 25(3), 1517; https://doi.org/10.3390/ijms25031517 - 26 Jan 2024

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Abstract

Diabetes mellitus is a devastating chronic metabolic disease. Since the majority of type 2 diabetes mellitus patients are overweight or obese, a novel term—diabesity—has emerged. The gut–brain axis plays a critical function in maintaining glucose and energy homeostasis and involves a variety of peptides. Amylin is a neuroendocrine anorexigenic polypeptide hormone, which is co-secreted with insulin from β-cells of the pancreas in response to food consumption. Aside from its effect on glucose homeostasis, amylin inhibits homeostatic and hedonic feeding, induces satiety, and decreases body weight. In this narrative review, we summarized the current evidence and ongoing studies on the mechanism of action, clinical pharmacology, and applications of amylin and its analogs, pramlintide and cagrilintide, in the field of diabetology, endocrinology, and metabolism disorders, such as obesity. Full article

(This article belongs to the Special Issue Drug Therapies for Diabetes)

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20 pages, 634 KiB

Open AccessReview

Drug Therapies for Diabetes

by Roni Weinberg Sibony, Omri Segev, Saar Dor and Itamar Raz

Int. J. Mol. Sci. 2023, 24(24), 17147; https://doi.org/10.3390/ijms242417147 - 5 Dec 2023

Cited by 3 | Viewed by 3222

Abstract

The treatment of type 2 diabetes (T2D) necessitates a multifaceted approach that combines behavioral and pharmacological interventions to mitigate complications and sustain a high quality of life. Treatment encompasses the management of glucose levels, weight, cardiovascular risk factors, comorbidities, and associated complications through medication and lifestyle adjustments. Metformin, a standard in diabetes management, continues to serve as the primary, first-line oral treatment across all age groups due to its efficacy, versatility in combination therapy, and cost-effectiveness. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) offer notable benefits for HbA1c and weight reduction, with significant cardiovascular benefits. Sodium-glucose cotransporter inhibitors (SGLT-2i) lower glucose levels independently of insulin while conferring notable benefits for cardiovascular, renal, and heart-failure outcomes. Combined therapies emphasizing early and sustained glycemic control are promising options for diabetes management. As insulin therapy remains pivotal, metformin and non-insulin agents such as GLP-1 RA and SGLT-2i offer compelling options. Notably, exciting novel treatments like the dual GLP-1/ glucose-dependent insulinotropic polypeptide (GIP) agonist show promise for substantially reducing glycated hemoglobin and body weight. This comprehensive review highlights the evolving landscape of pharmacotherapy in diabetes, the drugs currently available for treating diabetes, their effectiveness and efficacy, the impact on target organs, and side effects. This work also provides insights that can support the customization of treatment strategies. Full article

(This article belongs to the Special Issue Drug Therapies for Diabetes)

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19 pages, 836 KiB

Open AccessReview

Research Progress on the Relationship between Vitamins and Diabetes: Systematic Review

by Jiameng Liu, Luqi Qin, Jiahuan Zheng, Litao Tong, Wei Lu, Cong Lu, Jing Sun, Bei Fan and Fengzhong Wang

Int. J. Mol. Sci. 2023, 24(22), 16371; https://doi.org/10.3390/ijms242216371 - 15 Nov 2023

Viewed by 1666

Abstract

Diabetes is a serious chronic metabolic disease that causes complications over time, bringing serious public health challenges that affect different countries across the world. The current clinical drugs for diabetes may lead to adverse effects such as hypoglycemia and liver and abdominal distension and pain, which prompt people to explore new treatments for diabetes without side effects. The research objective of this review article is to systematically review studies on vitamins and diabetes and to explain their possible mechanism of action, as well as to assess the role of vitamins as drugs for the prevention and treatment of diabetes. To achieve our objective, we searched scientific databases in PubMed Central, Medline databases and Web of Science for articles, using “vitamin” and “diabetes” as key words. The results of numerous scientific investigations revealed that vitamin levels were decreased in humans and animals with diabetes, and vitamins show promise for the prevention and/or control of diabetes through anti-inflammation, antioxidation and the regulation of lipid metabolism. However, a few studies showed that vitamins had no positive effect on the development of diabetes. Currently, studies on vitamins in the treatment of diabetes are still very limited, and there are no clinical data to clarify the dose–effect relationship between vitamins and diabetes; therefore, vitamins are not recommended as routine drugs for the treatment of diabetes. However, we still emphasize the great potential of vitamins in the prevention and treatment of diabetes, and higher quality studies are needed in the future to reveal the role of vitamins in the development of diabetes. Full article

(This article belongs to the Special Issue Drug Therapies for Diabetes)

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21 pages, 2002 KiB

Open AccessReview

Novel Antidiabetic Agents and Their Effects on Lipid Profile: A Single Shot for Several Cardiovascular Targets

by Francesco Piccirillo, Sara Mastroberardino, Annunziata Nusca, Lorenzo Frau, Lorenzo Guarino, Nicola Napoli, Gian Paolo Ussia and Francesco Grigioni

Int. J. Mol. Sci. 2023, 24(12), 10164; https://doi.org/10.3390/ijms241210164 - 15 Jun 2023

Cited by 4 | Viewed by 3041

Abstract

Type-2 diabetes mellitus (DM) represents one of the most important risk factors for cardiovascular diseases (CVD). Hyperglycemia and glycemic variability are not the only determinant of the increased cardiovascular (CV) risk in diabetic patients, as a frequent metabolic disorder associated with DM is dyslipidemia, characterized by hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol levels and a shift towards small dense low-density lipoprotein (LDL) cholesterol. This pathological alteration, also called diabetic dyslipidemia, represents a relevant factor which could promotes atherosclerosis and subsequently an increased CV morbidity and mortality. Recently, the introduction of novel antidiabetic agents, such as sodium glucose transporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), has been associated with a significant improvement in CV outcomes. Beyond their known action on glycemia, their positive effects on the CV system also seems to be related to an ameliorated lipidic profile. In this context, this narrative review summarizes the current knowledge regarding these novel anti-diabetic drugs and their effects on diabetic dyslipidemia, which could explain the provided global benefit to the cardiovascular system. Full article

(This article belongs to the Special Issue Drug Therapies for Diabetes)

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