Diabetes Mellitus: New Challenges and Innovative Therapies

Sena, Cristina M.; Bento, Carla F.; Pereira, Paulo; Marquês, Filipa; Seiça, Raquel

doi:10.1007/978-94-007-5971-8_3

Cited by 11 publications

(11 citation statements)

References 269 publications

(117 reference statements)

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“…Diamyd ® has shown promising results in Phase I and Phase II clinical trials in humans and is currently conducting two clinical Phase III studies on type 1 diabetics. Diamyd ® can also be combined with other drugs that stimulate the production of new β cells, or with β -cell transplants [77].…”

Section: Gene Therapymentioning

confidence: 99%

See 1 more Smart Citation

Diabetes mellitus – an overview

Sonia¹,

Sharma²

2014

Oral Delivery of Insulin

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Section: Gene Therapymentioning

confidence: 99%

“…Slow-acting and rapid-acting insulin secretagogues are available [76]. The major side effects of insulin Chemical structure of oral hypoglycaemic drugs secretagogues (and insulin replacement) are hypoglycaemia and weight gain [77]. Examples of insulin secretagogues include sulfonylureas and meglitinides.…”

Section: Insulin Secretagoguesmentioning

confidence: 99%

Diabetes mellitus – an overview

Sonia¹,

Sharma²

2014

Oral Delivery of Insulin

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“…One of the most important metabolic complications in type-2 DM (T2D) is hyperglycemia which is associated with the development of nephropathy, retinopathy, neuropathy, and heart and blood vessel disease [3]. Preventing hydrolyzing of carbohydrates is a novel treatment method and alternative medicine for treating the T2D by a delay in the digestion of carbohydrates ultimately reducing the rate of glucose absorption [4,5]. α-Glu and α-Amy are hydrolyzing enzymes which secreted and placed in the small intestine and they are responsible for hydrolyzing dietary carbohydrates.…”

Section: Introductionmentioning

confidence: 99%

Anti-Diabetic Potential of Anti-Oxidant Compounds "Riboflavin, Flavin Mononucleotide and Flavin Adenine Dinucleotide" with High Therapeutic Potency through Inhibition of α-Amylase and α-Glucosidase Enzymes at Sub-Micromolar Concentrations

Esmaeili¹,

Amoushahi²,

Barati³

et al. 2020

SDRP JFST

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Diabetes is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time. Inhibition of carbohydrate hydrolyzing enzymes leads to decrease in the absorption of glucose which is considered as one of the effective managements of diabetes mellitus. Vegetable, fruit, milk, and fish are good sources of riboflavin (RF) and vitamin B5 with versatile health benefits. The well-adapted structural features of these compounds for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible backbone, and hydrophobic nature. The substrates of α-amylase (α-Amy) and α-glucosidase (α-Glu), known as key absorbing enzymes, have functional groups (OH groups) resembling RF and vitamin B5. Therefore, the present study was conducted to evaluate the inhibitory properties of fliavin, RF, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD) and vitamin B5 against α-Amy and α-Glu. The median inhibition concentration (IC50) values for α-Glu in the presence of RF, FMN and FAD were determined 136.7±4.8, 235.4±5.2 and 78.9±3.4, respectively. The IC50 values α-Amy in the presence of RF, FMN and FAD were determined 165.6±7.1, 253.6±5.5 and 131.2±6.3, respectively. Moreover, the Ki values of RF were calculated as 14.2±1.8 and 18.6±1.7 µM for α-Glu and α-Amy in a mixed-mode. In addition, to communicate with the active site of α-Glu and α-Amy respectively, RF presented a binding energy of -8.1 and -7.3 kcal/mol, FMN -7.1 and -6.8, and FAD -10.3 and -7.8 kcal/mol. These antioxidant inhibitors may be potential anti-diabetic drugs, not only to reduce glycemic index, but also to limit the activity of the major reactive oxygen species (ROS) producing pathways. Key words: Riboflavin, hydrolyzing enzymes, enzyme inhibition, hyperglycemia Introduction

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“…Hyperglycemia is one of the most important metabolic complications in type-2 DM (T2D) which lead to the development of nephropathy, retinopathy, neuropathy, heart and blood vessel diseases [3]. Preventing of hydrolyzing of carbohydrates is a novel treatment method and alternative medicine for treating T2D through delay in the digestion of carbohydrates ultimately reducing the rate of glucose absorption [4]. α-Amy and α-Glu are hydrolyzing enzymes secreted and placed in small intestine and they are responsible for hydrolyzing dietary carbohydrates.…”

Section: Introductionmentioning

confidence: 99%

The Inhibitory Effects of Nucleosides, Nicotinamide Adenine Dinucleotide, Adenosine 5'-Triphosphate, Inosine, Nicotinamide Riboside and Nicotinamide Mononucleotide Against α-Amylase and α-Glucosidase Enzymes

Ghorbani¹,

Ghorbani²,

Ghahghaee³

et al. 2020

SDRP JFST

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Diabetes is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time. Inhibition of carbohydrate hydrolyzing enzymes leads to decrease in the absorption of glucose which is considered as one of the effective managements of diabetes mellitus. Vegetable, fruit, milk and fish are good sources of nucleosides and inosine (INO), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) with versatile health benefits. The well-adapted structural features of these compounds for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible backbone and hydrophobic nature. The substrates of α-amylase (α-Amy) and α-Glucosidase (α-Glu), known as key absorbing enzymes, have functional groups (OH groups) resembling nucleosides. Therefore, the present study was conducted to evaluate the inhibitory properties of nucleosides against αAmy and α-Glu. The median inhibition concentration (IC50) values for α-Glu in the presence of adenosine (ADN), adenosine triphosphate (AMP), NR, INO, adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), Adenosine diphosphate (ADP)-ribose, ADP-glucose and NMN were determined 208.6±3.8, 254.1±5.2, 177.7±4.8, 192.1±5.2, 215.9±2.7, 65.4±1.3, 63.4±2.2, 75.6±4.2 and 196.1±2.6, respectively. The IC50 values α-Amy in the presence of ADN, AMP, NR, INO, ATP, NAD, ADP-ribose, ADP-glucose and NMN were determined 145.3±2.4, 202.3±3.9, 127.7±4.8, 163.5±3.6, 185.3±1.2, 80.4±2.8, 64.8±4.7, 51.1±1.6 and 166.5±1.4, respectively. Moreover, the Ki values of NAD were calculated as 13.8±0.8 and 18.6±2.4 µM for α-Glu and α-Amy in a competitive-mode and noncompetitive -mode inhibition. In addition, to communicate with the active site of α-Glu and α-Amy respectively, NR presented a binding energy of -7.8 and -6.8 kcal/mol, INO -7.3 and -6.9, ATP -8.3 and -7.3, NAD -10.0 and -8.5, ADP-ribose -8.7 and -7.4, ADP-glucose -8.9 and -7.6, cAMP -6.6 and -6.3 and NMN -6.8 and -7.0 kcal/mol. These antioxidant inhibitors may be potential anti-diabetic drugs, not only to reduce glycemic index, but also to limit the activity of the major reactive oxygen species (ROS) producing pathways. Key words: Nucleosides, NAD, hydrolyzing enzymes, enzyme inhibition, hyperglycemia

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Diabetes Mellitus: New Challenges and Innovative Therapies

Cited by 11 publications

References 269 publications

Diabetes mellitus – an overview

Diabetes mellitus – an overview

Anti-Diabetic Potential of Anti-Oxidant Compounds "Riboflavin, Flavin Mononucleotide and Flavin Adenine Dinucleotide" with High Therapeutic Potency through Inhibition of α-Amylase and α-Glucosidase Enzymes at Sub-Micromolar Concentrations

The Inhibitory Effects of Nucleosides, Nicotinamide Adenine Dinucleotide, Adenosine 5'-Triphosphate, Inosine, Nicotinamide Riboside and Nicotinamide Mononucleotide Against α-Amylase and α-Glucosidase Enzymes

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