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Hedgehog Signaling Pathway

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...

Hedgehog Signaling Pathway

Hedgehog Signaling Pathway

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

Notch Signaling Pathway

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...

Hormones Regulating Blood Glucose

Hormones Regulating Blood Glucose

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.
In addition to accelerating glucose uptake and utilization, insulin has...

Endocrine Signaling

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Related Experiment Video

Updated: Mar 21, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

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Published on: January 4, 2018

Systemic Sonic Hedgehog Signaling Links Intestinal Nutrient Sensing With Sex-Specific Type 2 Diabetes Progression.

Johannes Alfredsson^1,2, Nayere Taebnia³, Najat Dzaki⁴

¹Department of Microbiology and Immunology, Gothenburg University, Gothenburg, Sweden.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology

|March 19, 2026

Summary

Sonic Hedgehog (Shh) signaling impacts metabolic homeostasis. Elevated Shh levels are linked to type 2 diabetes and hypertension in females, suggesting a sexually dimorphic role in metabolic dysfunction.

Keywords:

Sonic Hedgehog circulation female insulin resistance organoids plasma prediabetes sex differences small intestine type 2 diabetes

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Last Updated: Mar 21, 2026

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

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Published on: January 4, 2018

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Published on: February 6, 2020

Area of Science:

Endocrinology and Metabolism
Molecular Biology
Human Physiology

Background:

Systemic Sonic Hedgehog (Shh) signaling is implicated in metabolic homeostasis.
Its precise role in human metabolic diseases, including type 2 diabetes, requires further definition.

Purpose of the Study:

To investigate the association of plasma Shh levels with common non-communicable diseases, particularly type 2 diabetes mellitus (T2DM) and metabolic dysfunction.
To explore the sex-specific differences in these associations.

Main Methods:

Plasma Shh levels were measured in two large Swedish cohorts (n=735).
Associations with T2DM, hypertension, and insulin resistance were analyzed.
Mechanistic studies utilized human intestinal organoids to assess Shh secretion in response to glucose and insulin.

Main Results:

Substantial inter-individual variability in Shh levels was observed.
Elevated Shh levels were associated with T2DM and hypertension in females, but not males.
Shh levels correlated with insulin resistance, reflecting distinct pathophysiological states in males (compensatory insulin secretion) and females (β-cell dysfunction).
Human intestinal organoids showed Shh secretion induced by glucose and insulin.

Conclusions:

Shh is a sexually dimorphic marker of metabolic dysfunction.
Systemic Shh signaling, potentially originating from the intestine, plays a functional role in glycemic control and metabolic disease.