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Related Concept Videos

Hormones Regulating Blood Glucose01:16

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Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Hypoglycemia and Glucagon01:15

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Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
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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.
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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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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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Updated: Feb 19, 2026

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
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Engineering Glucose Responsiveness Into Insulin.

Niels C Kaarsholm1, Songnian Lin1, Lin Yan1

  • 1Merck Research Laboratories, Merck & Co., Inc., Kenilworth, NJ.

Diabetes
|November 4, 2017
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel "smart" insulin, MK-2640, that adjusts its clearance based on blood glucose levels. This innovation aims to improve glycemic control while significantly reducing the risk of hypoglycemia in diabetic patients.

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Endocrinology

Background:

  • Insulin therapy for diabetes has a narrow therapeutic index, posing a risk of hypoglycemia due to constant insulin clearance.
  • Exogenous insulin clearance is independent of blood glucose, exacerbating hypoglycemia risk.

Purpose of the Study:

  • To develop a glucose-responsive "smart" insulin that modulates its own clearance.
  • To mitigate hypoglycemia risk by linking insulin action to blood glucose levels.

Main Methods:

  • Engineered insulin analogs (MK-2640) with affinity for both the insulin receptor (IR) and mannose receptor C-type 1 (MR).
  • Evaluated MK-2640's glucose-dependent clearance in canine glucose clamp studies.
  • Assessed therapeutic index of MK-2640 versus regular insulin in diabetic minipig dose-escalation studies.

Main Results:

  • MK-2640 clearance via MR increased as plasma glucose decreased, reducing its availability to the IR by ~30% in dogs.
  • MK-2640 demonstrated a threefold higher therapeutic index compared to regular insulin (1.3-fold) in diabetic minipigs.

Conclusions:

  • The novel saccharide-modified insulin analog, MK-2640, exhibits glucose-dependent pharmacokinetics.
  • MK-2640 shows potential as a safer insulin therapy with an improved therapeutic index, reducing hypoglycemia risk.