Related Experiment Video

Updated: Jun 20, 2026

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

Critical roles for the TSC-mTOR pathway in β-cell function

Hiroyuki Mori1, Ken Inoki, Darren Opland

  • 1Dept. of Pharmacology and Moores Cancer Center, Univ. of California San Diego, La Jolla, CA 92093-081, USA. kuguan@ucsd.edu

American Journal of Physiology. Endocrinology and Metabolism
|August 20, 2009
PubMed

Insights

Loss of TSC1 in pancreatic beta cells enhances mTORC1 signaling, leading to larger cells and improved insulin production. This promotes better glycemic control, highlighting mTOR

Area of Science:

  • Cell Biology
  • Metabolism
  • Endocrinology

Background:

  • TSC1 (Tuberous Sclerosis Complex 1) acts as a tumor suppressor by inhibiting mTORC1 signaling.
  • mTORC1 (mammalian target of rapamycin complex 1) is a key regulator of cell growth and anabolic processes.
  • Dysregulation of TSC1 and mTORC1 pathways can impact cellular function and organismal metabolism.

Purpose of the Study:

  • To investigate the role of TSC1 and mTORC1 in pancreatic beta-cell function.
  • To determine the impact of TSC1 loss on beta-cell size, mass, and insulin production.
  • To elucidate the downstream signaling pathways affected by TSC1 loss in beta-cells.

Main Methods:

  • Generation of mice with Tsc1 specifically deleted in pancreatic beta-cells (Rip-Tsc1cKO mice) using Rip2/Cre.
  • Analysis of young and older Rip-Tsc1cKO mice for metabolic and beta-cell phenotypes.
  • Assessment of beta-cell proliferation, apoptosis, size, mass, and insulin production.
  • Evaluation of Akt signaling pathway activation in beta-cells.

Main Results:

  • Young Rip-Tsc1cKO mice exhibited enhanced beta-cell function, including increased beta-cell size, mass, and insulin production, leading to improved glycemic control.
  • These effects were mediated by mTORC1 signaling, independent of changes in beta-cell proliferation or apoptosis.
  • Impaired Akt signaling was observed in the beta-cells of Rip-Tsc1cKO mice, yet mTORC1 signaling remained dominant.
  • Older Rip-Tsc1cKO animals developed obesity due to hypothalamic Tsc1 excision.

Conclusions:

  • mTORC1 signaling is a critical anabolic driver of pancreatic beta-cell size and insulin production.
  • The TSC1-TSC2-Rheb-mTORC1 pathway plays a crucial role in maintaining beta-cell function and glycemic control.
  • Targeting mTORC1 signaling in beta-cells may offer therapeutic potential for metabolic disorders.

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds12:32

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds

Published on: January 23, 2018

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

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 this inhibition is released...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...