Phytotherapy in the Management of Diabetes and Hypertension: Volume 3

Mohamed Edouks

• Publisher: Bentham Science Publishers
• Year: 2020
• ISBN:
  9789811459139
• Topic: Medicine
• Subtopic: Endocrinology & Metabolism

Medicinal plants are a source of potential therapeutic compounds. Phytotherapycan give patients long term benefits with less or no side effects. This is the thirdvolume of the series which features monographs on selected natural productsused to treat diabetes and hypertension. This volume brings 7 chapterscontributed by 22 researchers, that cover updates on the biochemistry ofdiabetes, information on anti-diabetic and antihypertensive properties of oil bearingplants, herbs, fruits and vegetables, medicinal plants from Asia, as well as the medicinal valueof specific plants such as, star apple (Chrysophyllum cainito).In terms of therapeutic agents, two reviews in this volume focus on terpenoidsand glucagon-like peptide – 1 are also included.Each review covers different plant species or medicinal agents whereapplicable, providing readers essential information about their role in thetreatment of diabetes and hypertension.Both academic and professional pharmacologists as well as clinicianswill find comprehensive information on a variety of therapeutic agents in thisvolume.

Management of Diabetes Mellitus by Natural Products: Glucagon-like Peptide 1 Perspective

Ojaskumar D. Agrawal^{1, 2}, Yogesh A. Kulkarni^{1, *}

¹ Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, V.L Mehta Road, Vile Parle (W), Mumbai – 400 056, India

² Vivekanand Education Society’s College of Pharmacy, Chembur (E), University of Mumbai, Mumbai 400074, India

Abstract

Diabetes Mellitus (DM) has become a major and serious health problem worldwide. To overcome this lifestyle disease, natural products can be explored systematically. These natural products act on various targets and show their effect in diabetic conditions. Out of this, GLP-1 Receptor is one of the promising targets. Cells in the small intestine secrete Incretin hormones upon nutrient ingestion. Glucagon-like peptide-1 (GLP-1) is a primary incretin hormone in metabolism that has a potent antihyperglycemic effect. Insulin will release, in the presence of hyperglycemia, GLP-1 stimulates the pancreas to release insulin, stops glucagon release, gastric emptying slows down and increases satiety by acting on the hypothalamus. Storage of GLP-1 is mainly in secretory granules of L cells, in small intestinal distal portion and colon. When the cells are activated, this peptide is released into the main bloodstream.GLP-1 secreted mainly upon the ingestion of oral glucose or the ingestion of a mixed meal. Other factors like neurotransmitters and intestinal hormones also affect GLP-1 secretion from the intestine. Considering the above-mentioned parameters, regulation and control of GLP-1 are necessary as GLP-1 secretion is hampered in T2DM.

The present chapter focuses on scientific information about natural products specifically acting as GLP- 1 Receptor Agonist (GLP-1 RA).

Keywords: Diabetes Mellitus, GLP-1 Receptor Agonist, Herbal Medicine, Insulinotropic, Natural Products.

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^* Corresponding author Yogesh A. Kulkarni: Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS, V.L Mehta Road, Vile Parle (W), Mumbai – 400 056, India;
E-mail: [email protected]

INTRODUCTION

The number of individuals suffering from diabetes has reached 425 million. International Diabetes Federation data shows that in 2045 there will be 629 million people affected with diabetes. At the global level, India is going to be one

of the major countries having a large number of diabetic patients. Regular exercise and a healthy lifestyle can reduce the risk of this disease. The invention of a new drug molecule which is safer and better than the existing one, newer methodology and approach is need of an hour. All these invented drugs will help in reducing diabetes and its complications and as a result decrease in mortality and morbidity [1, 2].

Synthetic antidiabetic drugs have drawbacks like poor bioavailability, the too short or too long half-life, low therapeutic index, non – linear kinetics because of saturable clearance mechanism, on repeat, dosing increased clearance because of auto induction, multiple metabolites not covered by toxicity studies [1].

Considering the above points, there is utmost need to find out more efficacious, better and safer alternatives in the management of diabetes [2]. In recent years various natural products have been evaluated and proved for their beneficial effects in the management of diabetes.

In the ancient era, medicinal plants which are collected from the forest were only the basic source of drugs for all types of ailments. Hence more Weightage is given to these traditional and herbal drugs which can be used to treat all types of diseases. Thus medicinal natural products are playing a crucial role in the management of health care. Over twelve hundred medicinal plants have been identified and have been claimed as a remedy for diabetes and out of those, several hundred have been evaluated for the said treatment [3]. Several synthetic compounds have been discovered from medicinal plants like metformin, which was based on biguanide compound from plant Galanga officinalis [3]. Throughout the world, more than 400 plants, over 700 recipes and compounds have been broadly evaluated for T2D treatment [4]. In the human body, these natural products act on various targets and show their effects.

Glucagon-Like Peptide - 1

Upon oral glucose intake, gastrointestinal tract secretes incretin hormones [5]. These are gut peptides generally secreted after food intake and augment insulin secretion. Incretin hormones like Glucose-dependent insulinotropic polypeptide and Glucagon-Like Peptide -1 are secreted by upper K cells and lower enteroendocrine L cells of gut respectively.

Also, GLP-1 has different and multiple effects on different organs. GLP-1 is responsible for decreasing apatite which is linked with food intake and weight loss. GLP-1 is synthesized from the posttranslational modification of proglucagon, by Prohormone Convertase 1 (PC1). It stimulates Glucose Stimulated Insulin Secretion (GSIS) when glucose and free fatty acids are taken orally [6]. It has been reported that GLP-1 has insulinotropic action. High sugar intake results in increased GLP-1 secretion and ultimately in the stimulation of β-cells which secrets insulin. This proves that GLP-1 mimetics or its receptor agonists can be used for the management of diabetes [7].

Chemically, GLP-1 is available in two forms: GLP-1 (7–36) amide (80% of circulating GLP-1) and GLP-1 (7–37) amide. GLP-1 (1–36 amide) is predominantly secreted in the pancreas, whereas GLP-1 (1–37) is secreted in the ileum and hypothalamus [8^-13].

Secretion of Incretin Hormones in Healthy Human Subjects

Carbohydrates like glucose and sucrose, starch; amino acids, triglycerides and proteins stimulate the secretion of GLP-1.

Proteins serve as a relatively weak stimulus for GLP-1 secretion. For this purpose, a minimum fixed rate of gastric emptying is required to have measurable secretion. Despite the distal location of secretory L cells in the gut, GLP-1 will be secreted immediately after ingestion of nutrients and meals [14].

Deacon and Holst identified that for degradation of GLP-1, dipeptidyl peptidase 4 (DPP-4) enzyme in plasma is responsible [15] and also showed that this degradation could be prevented by inhibiting enzyme DPP-4 [16]. GLP-1 has a very short half-life (<2 min) because of its speedy cleavage by Dipeptidyl peptidase-4 (DPP-4) [7]. Studies on pigs showed that practically it was possible to prevent degradation of GLP-1 by DPP-4 and this action showed a marked increase in insulin in response to glucose and GLP-1 [17].

GLP-1 affects levels of insulin and glucagon to decrease elevated blood sugar levels in two ways. First GLP-1 increases the body's natural insulin secretion in response to a meal and second GLP-1 lowers levels of the hormone glucagon after eating. Glucagon works opposite to insulin and raises blood sugar levels’, so decreasing glucagon level helps to lower blood sugar. For insulin produc...