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Related Concept Videos

Insulin: Biosynthesis, Chemistry, and Preparation01:25

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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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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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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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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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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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In most cases, excessive hormone production is prevented by negative feedback—a loop that starts with a stimulus inducing the release of a particular substance, like a hormone, to maintain a certain level before triggering a signal that results in a decrease in further release of the hormone.
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β-cell-mimetic designer cells provide closed-loop glycemic control.

Mingqi Xie1, Haifeng Ye2, Hui Wang1

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Researchers engineered human cells into "designer cells" that mimic pancreatic beta cells. These cells effectively managed blood glucose levels in mice, offering a potential new therapy for diabetes mellitus.

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Area of Science:

  • Biotechnology
  • Endocrinology
  • Synthetic Biology

Background:

  • Diabetes mellitus involves chronically deregulated blood glucose due to beta cell loss (T1D) or impaired insulin sensitivity and release (T2D).
  • Current treatments often struggle with long-term glucose control and complications.

Purpose of the Study:

  • To develop therapeutically applicable, glucose-responsive "designer cells" using minimal human cell engineering.
  • To establish synthetic biological systems for treating type 1 and type 2 diabetes.

Main Methods:

  • Engineered human cells with a synthetic circuit coupling glycolysis-mediated calcium entry to an excitation-transcription system.
  • Controlled therapeutic transgene expression in response to glucose levels.
  • Implanted engineered cells in mouse models of type 1 and type 2 diabetes.

Main Results:

  • Implanted designer cells corrected insulin deficiency and normalized hyperglycemia in type 1 diabetes mice.
  • Engineered cells expressing glucagon-like peptide 1 improved glucose tolerance and insulin release in type 2 diabetes mice.
  • Demonstrated self-sufficient glucose regulation and therapeutic transgene expression.

Conclusions:

  • Minimal engineering of human cells can create functional beta-cell-mimetic designer cells.
  • Synthetic biological circuits offer a viable strategy for diabetes mellitus therapy.
  • These systems hold potential for combined diagnosis and treatment of diabetes.