Editor: Madhukar Saxena

Pharmacological and Molecular Perspectives on Diabetes

eBook: US $49 Special Offer (PDF + Printed Copy): US $90
Printed Copy: US $65
Library License: US $196
ISBN: 978-981-5040-23-4 (Print)
ISBN: 978-981-5040-22-7 (Online)
Year of Publication: 2022
DOI: 10.2174/97898150402271220101

Introduction

Pharmacological and Molecular Perspectives on Diabetes is a compilation of reviews on clinical and scientific aspects of diabetes mellitus. It presents 11 contributions by eminent scholars that give the reader rational pharmacological and genetic perspectives of the disease and its treatment. The reviews approach diabetes from different angles, and highlight research that has been done to understand some questions about the molecular biology of diabetes in experimental settings. Topics of clinical significance such as the use of different hypoglycemic agents, and diabetic complications in clinical settings are also covered.

Topics included in this book are:

- Epigenetic alterations and type 2 diabetes mellitus

- Responses to nutritional chromium supplements for type 2 diabetes mellitus

- Endocrine role of osteocalcin in homeostatic regulation of glucose metabolism

- Effect of diabetes on memory

- Osteoarthritis in relation to type 2 diabetes mellitus: prevalence, etiology, symptoms and molecular mechanism

- Infection of novel coronavirus in patients with diabetes mellitus

- Role of an anti-inflammatory agent in the management of type 2 diabetes mellitus

- Role of antidiabetic agents which helps regulates TCF7L2 variations in type 2 diabetes mellitus

- Relationship between type 2 diabetes mellitus, PCOD and neurological disorders: role of antidiabetic drugs

- Comparison of different types of insulin available for type 1 diabetes treatment

- Circadian rhythm disruption: special reference to type 2 diabetes mellitus

- Type 2 diabetes mellitus and its complications: pharmacogenetics based correlations and circulating microRNA as biomarkers

Pharmacological and Molecular Perspectives on Diabetes should prove to be of interest to all pharmaceutical and molecular biology scientists who are involved in research in anti-diabetic drug design and discovery, and practicing endocrinologists who wish to keep abreast of recent developments in the field.

Audience: Students and researchers in life sciences, medicine and pharmacology; endocrinologists and diabetologists.

Preface

Type 2 diabetes mellitus (T2DM) is one of the most challenging public health issues of the 21st century. T2DM, a complex polygenic metabolic disorder, is characterized both by hyperglycemia and hyperinsulinemia resulting from the interplay of genetic/epigenetic along with environmental factors. Epigenetic alterations present in T2DM patients and not in normal healthy individuals may give an insight into how environmental factors might contribute to T2DM. Epigenetic mechanisms involve DNA methylation, histone modification, and gene expression alterations via micro RNAs (miRNA). These changes lead to glucose intolerance, insulin resistance, β-cell dysfunction, and ultimately T2DM. Extensive studies based on alterations in gene expression associated with DNA methylation/histone modifications are required to elucidate the relationship between vital environmental factors and T2DM progression. Candidate genes responsible for inter-individual differences in antidiabetic responses may also undergo epigenetic alterations. Identification and characterization of such epigenetic biomarkers may help in the prediction of T2DM risk as well as response to antidiabetic treatment and form an essential part of personalized medicine. The results of many clinical studies support the view that chromium can improve both insulin and glucose metabolism in patients with T2DM, especially in the form of dietary supplements (chromium picolinate). However, insufficient data are available to create a conclusive hypothesis that nutritional supplements of chromium could be useful for the treatment of T2DM, and thus there is no need to endorse a general prescription for the management of diabetes using these supplements. Chromium supplements have minimal usefulness based on the lower impact of established evidence, and there is no reason for promoting their use for glycemic control in patients with existing T2DM. Well-designed, high-quality, broad, and long-term trials are required to improve the current data and ensure the protection and efficacy of drugs. Osteocalcin, a well-known bone formation marker, is secreted from osteoblasts and exists in fully carboxylated, partially carboxylated, and completely uncarboxylated forms. The endocrine involvement of uncarboxylated osteocalcin in glucose homeostasis has recently been confirmed. It has been demonstrated that double recessive osteocalcin mutant mice are hyperglycemic and hypoinsulinemic, have reduced β cell numbers, and are insulin resistant. In contrast, leptin (an adipocyte-derived hormone) indirectly regulates the secretion of insulin in part through the inhibition of osteocalcin conversion to uncarboxylated form via β2 adrenergic receptor signaling in osteoblasts. Diabetes exerts widely known noxious effects on the kidney and blood vessels. Besides these effects, it also causes damages to the nerve cells and glial cells in the brain that result in impaired memory. The altered memory formation in patients with diabetes might be due to Alzheimer's, stroke, and high sugar levels in the blood. Among all of the above parameters, damage to blood vessels is most common. Although both diabetes and Alzheimer's patients share common symptoms so it can be concluded that diabetes might cause an increased risk of development of AD. However, pioneer studies have found that coronavirus disease 2019 (COVID-19) has shown severity in patients with diabetes mellitus. COVID-19 may potentially cause hyperglycemia in patients who have been exposed to it. Along with other risk factors, high blood glucose may also affect immune and inflammatory responses, thus inclining patients to severe COVID-19 with a much higher mortality rate. Angiotensin-converting enzyme 2 (ACE2) receptors are the common entry point for SARS-CoV-2. Recent findings suggest dipeptidyl peptidase 4 (DPP4) can also act as a binding and entry target. Glucose-lowering agents and anti-viral treatments can alter the risk, but there exist limitations to their use, and its possible interactions with COVID-19 treatments should be carefully assessed. Most of these conclusions are preliminary, and further investigation of the optimal management in patients with diabetes mellitus is warranted. Evidence from the literature shows that in T2D, alterations in the level of cytokine inflammatory gene (IL-1, IL-6, TNF-a) expression increased while anti-inflammatory gene (IL-1Ra, IL-4, IL-10, and IL-13) expression decreased. Various physical activities like weight loss and exercise are beneficial for patients with T2D. Many anti-diabetic drugs are effective against type 2 diabetes in which liraglutide, sulfonylureas, and salsalate drugs exert an anti-inflammatory action in obese patients with type 2 diabetes. They all have a potent anti-inflammatory effect due to the inhibition of the NF-kB pathway, the upregulation of SIRT1 expression, and down-regulation of pro-inflammatory factors, including cytokines (TNF-α, IL-1β, and IL-6. Current insulin therapies more closely mimic the normal physiologic insulin secretion by the pancreas, which gives a better-glycosylated hemoglobin level in patients suffering from diabetes. This chapter includes the many types of insulins and their regimens, the classification of insulin types, which insulin is best for different age groups, the diet to follow, the principles of dose adjustment, and an overview of insulin pump therapy. Thus, it seems the need of the hour to focus on chronopathology and chronomedicine as alternative treatment strategies to manage and prevent T2DM, which can further contribute to the reduction of the risks of metabolic co-morbidities in the human population.

Madhukar Saxena

Department of Biotechnology
Babasaheb Bhimrao Ambedkar University
Lucknow
India