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Related Concept Videos

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.
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Glucagon-like Receptor Agonists01:24

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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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Diabetes Mellitus: Overview and Type I Subtype01:22

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Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
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Insulin: Dosing Regimen and Adverse Effects01:16

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Insulin-replacement therapy usually includes both long-acting insulin (basal) and short-acting insulin (to cater to postprandial needs). In a diverse group of type 1 diabetes patients, the average daily insulin dose is typically 0.5-0.7 units/kg body weight. However, obese patients and pubertal adolescents may need more due to insulin resistance.
The basal dose constitutes about 40%-50% of the total daily dose, with the rest as premeal insulin. The mealtime insulin dose should mirror...
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Insulin: The Receptor and Signaling Pathways01:28

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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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Diabetes: Management and Pharmacotherapy01:15

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The therapy for diabetes aims to alleviate hyperglycemia-related symptoms, prevent acute metabolic decompensation, and reduce chronic end-organ complications. Glycemic control is evaluated through short-term (self-monitoring, continuous glucose monitoring) and long-term (A1c, fructosamine) metrics, enabling near real-time tracking of blood glucose levels and reflecting glycemic control over specific time frames.
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Developing Insulin and BDNF Mimetics for Diabetes Therapy.

Chi Bun Chan1, Palak Ahuja1, Keqiang Ye2

  • 1School of Biological Sciences, The University of Hong Kong, Hong Kong.

Current Topics in Medicinal Chemistry
|October 30, 2019
PubMed
Summary

Developing non-peptidyl chemicals to mimic insulin or brain-derived neurotrophic factor (BDNF) offers a promising oral therapy for type 2 diabetes. These "pills" aim to overcome limitations of protein-based treatments for improved glucose control.

Keywords:
BDNFDiabetesInsulinMimeticObesityT2DM.

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Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Molecular Biology

Background:

  • Type 2 diabetes mellitus (T2DM) is a global health issue, often linked to obesity.
  • Current T2DM therapies focus on enhancing insulin signaling, but late-stage disease requires insulin replacement.
  • Reduced circulating brain-derived neurotrophic factor (BDNF) in T2DM suggests its potential therapeutic role.

Purpose of the Study:

  • To review the development of non-peptidyl small molecules that mimic insulin and BDNF.
  • To explore the potential of these novel compounds as orally active anti-diabetic agents.
  • To address the limitations of current protein-based insulin and BDNF therapies.

Main Methods:

  • Literature review of current research on non-peptidyl chemical mimetics.
  • Analysis of studies investigating insulin and BDNF signaling pathways in T2DM.
  • Evaluation of the therapeutic potential and challenges of small molecule drug development.

Main Results:

  • Non-peptidyl chemicals are being developed to replicate the functions of insulin and BDNF.
  • These small molecules offer potential for oral administration, overcoming protein limitations.
  • Research indicates these mimetics could offer a more convenient and effective T2DM treatment.

Conclusions:

  • Orally active non-peptidyl insulin and BDNF mimetics represent a significant advancement in T2DM therapeutics.
  • These agents have the potential to improve glucose homeostasis and address unmet clinical needs.
  • Further development is crucial for translating these findings into effective patient treatments.