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Related Concept Videos

Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
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Dipeptidyl Peptidase 4 Inhibitors01:23

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Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
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Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

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Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
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Insulin: Biosynthesis, Chemistry, and Preparation01:25

Insulin: Biosynthesis, Chemistry, and Preparation

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The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
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Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

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α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
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Oral Hypoglycemic Agents: Glinides01:06

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Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
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Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
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Rationally designed small peptides targeting DPP-4: Identification of potent anti-diabetic agents.

Sombir Jaglan1, Palwinder Singh1, Sheetal Vermani1

  • 1Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.

Bioorganic Chemistry
|July 23, 2025
PubMed
Summary

Researchers developed novel peptide-based inhibitors targeting dipeptidyl peptidase-4 (DPP-4) to treat type 2 diabetes. Compound 8 demonstrated potent DPP-4 inhibition and effectively lowered blood glucose in diabetic rats.

Keywords:
Dipeptidyl peptidase-4Drug-likenessGlucoseHistopathologyMolecular modellingPeptidesType 2 diabetes mellitus

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Area of Science:

  • Medicinal Chemistry
  • Endocrinology
  • Pharmacology

Background:

  • Dipeptidyl peptidase-4 (DPP-4) inhibition is a key strategy for managing type 2 diabetes.
  • Developing novel, potent, and safe DPP-4 inhibitors remains an active area of research.

Purpose of the Study:

  • To design and synthesize novel peptide-based inhibitors of DPP-4.
  • To evaluate the in vitro and in vivo efficacy and safety of the synthesized compounds as anti-diabetic agents.

Main Methods:

  • Synthesis and characterization of eighteen peptide-based DPP-4 inhibitors.
  • In vitro enzyme inhibition assays to determine IC50 values.
  • In vivo studies using streptozotocin/nicotinamide-induced diabetic Wistar rats.
  • Assessment of pharmacokinetic (ADME) and safety profiles.
  • Molecular docking and binding energy calculations (MM-GBSA) for selectivity analysis.

Main Results:

  • Compound 8 exhibited significant DPP-4 inhibitory activity with an IC50 of 0.12 nM.
  • Compound 8 demonstrated favorable drug-likeness properties, including good solubility and plasma stability.
  • In vivo administration of Compound 8 normalized glucose levels and improved lipid profiles, liver enzymes, and renal parameters in diabetic rats.
  • Histopathological analysis confirmed the protective effects of Compound 8 on kidney and pancreas tissues.
  • Compound 8 showed high selectivity for DPP-4 over related proteases DPP-8 and DPP-9, indicated by binding energy calculations.

Conclusions:

  • Peptide-based DPP-4 inhibitors represent a promising therapeutic approach for type 2 diabetes.
  • Compound 8 is a potent and selective DPP-4 inhibitor with significant anti-diabetic effects and a favorable safety profile.
  • Further investigation of Compound 8 is warranted for its clinical development as a novel anti-diabetic drug.