scholarly journals Growth control through regulation of insulin-signaling by nutrition-activated steroid hormone

2017 ◽  
Author(s):  
Kurt Buhler ◽  
Jason Clements ◽  
Mattias Winant ◽  
Veerle Vulsteke ◽  
Patrick Callaerts
Keyword(s):  
Insulin Signaling ◽  
Growth Regulation ◽  
Fat Body ◽  
Insulin Signalling ◽  
Steroid Hormone ◽  
Growth Control ◽  
Important Variable ◽  
Growth Defects ◽  
Insulin Producing Cells ◽  
Growth Promoting

AbstractGrowth and maturation are coordinated processes in all animals. Integration of internal cues, such as signalling pathways, with external cues such as nutritional status is paramount for an orderly progression of development in function of growth. In Drosophila, this coordination involves insulin and steroid signalling, but the mechanisms by which this occurs and how they are coordinated are incompletely understood. We show that production of the bioactive 20-hydroxyecdysone by the enzyme Shade in the fat body is a nutrient-dependent process. We demonstrate that during fed conditions, Shade plays a role in growth regulation, as knockdown of shade in the fat body resulted in growth defects and perturbed expression and release of the Drosophila insulin-like peptides from the insulin-producing cells (IPCs). We identify the trachea and IPCs as direct targets through which 20-hydroxyecdysone regulates insulin-signaling. The identification of the trachea-dependent regulation of insulin-signaling exposes an important variable that may have been overlooked in other studies focusing on insulin-signaling in Drosophila. Finally, we show with IPC-specific manipulations that 20E may both be a growth-promoting and growth-inhibiting signal in the IPCs acting through different nuclear receptors. Our findings provide a potentially conserved, novel mechanism by which nutrition can modulate steroid hormone bioactivation, reveal an important caveat of a commonly used transgenic tool to study IPC function and yield further insights as to how steroid and insulin signalling are coordinated during development to regulate growth and developmental timing.

scholarly journals Edem1 activity in the fat body regulates insulin signalling and metabolic homeostasis in Drosophila

2021 ◽  
Vol 4 (8) ◽  
pp. e202101079
Author(s):  
Himani Pathak ◽  
Jishy Varghese
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Quality ◽  
Fat Body ◽  
Insulin Signalling ◽  
Nutrient Status ◽  
Vital Role ◽  
Metabolic Homeostasis ◽  
Humoral Factors ◽  
Insulin Producing Cells ◽  
Factor Α

In Drosophila, nutrient status is sensed by the fat body, a functional homolog of mammalian liver and white adipocytes. The fat body conveys nutrient information to insulin-producing cells through humoral factors which regulate Drosophila insulin-like peptide levels and insulin signalling. Insulin signalling has pleiotropic functions, which include the management of growth and metabolic pathways. Here, we report that Edem1 (endoplasmic reticulum degradation–enhancing α-mannosidase–like protein 1), an endoplasmic reticulum–resident protein involved in protein quality control, acts in the fat body to regulate insulin signalling and thereby the metabolic status in Drosophila. Edem1 limits the fat body–derived Drosophila tumor necrosis factor-α Eiger activity on insulin-producing cells and maintains systemic insulin signalling in fed conditions. During food deprivation, edem1 gene expression levels drop, which aids in the reduction of systemic insulin signalling crucial for survival. Overall, we demonstrate that Edem1 plays a vital role in helping the organism to endure a fluctuating nutrient environment by managing insulin signalling and metabolic homeostasis.

scholarly journals FOXO-regulated transcription restricts overgrowth of Tsc mutant organs

2008 ◽  
Vol 180 (4) ◽  
pp. 691-696 ◽  
Author(s):  
Kieran F. Harvey ◽  
Jaakko Mattila ◽  
Avi Sofer ◽  
F. Christian Bennett ◽  
Matthew R. Ramsey ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Mammalian Cells ◽  
Growth Regulation ◽  
Pathway Activity ◽  
Tor Pathway ◽  
Diverse Species ◽  
Elevated Expression ◽  
Transcriptional Changes ◽  
Growth Promoting ◽  
Inactivating Mutations

FOXO is thought to function as a repressor of growth that is, in turn, inhibited by insulin signaling. However, inactivating mutations in Drosophila melanogaster FOXO result in viable flies of normal size, which raises a question over the involvement of FOXO in growth regulation. Previously, a growth-suppressive role for FOXO under conditions of increased target of rapamycin (TOR) pathway activity was described. Here, we further characterize this phenomenon. We show that tuberous sclerosis complex 1 mutations cause increased FOXO levels, resulting in elevated expression of FOXO-regulated genes, some of which are known to antagonize growth-promoting pathways. Analogous transcriptional changes are observed in mammalian cells, which implies that FOXO attenuates TOR-driven growth in diverse species.

scholarly journals Growth control through regulation of insulin signalling by nutrition-activated steroid hormone in Drosophila

Development ◽  
2018 ◽  
Vol 145 (21) ◽  
pp. dev165654 ◽  
Author(s):  
Kurt Buhler ◽  
Jason Clements ◽  
Mattias Winant ◽  
Lenz Bolckmans ◽  
Veerle Vulsteke ◽  
...  
Keyword(s):  
Insulin Signalling ◽  
Steroid Hormone ◽  
Growth Control

scholarly journals The Arabidopsis Root Tip (Phospho)Proteomes at Growth-Promoting versus Growth-Repressing Conditions Reveal Novel Root Growth Regulators

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1665
Author(s):  
Natalia Nikonorova ◽  
Evan Murphy ◽  
Cassio Flavio Fonseca de Lima ◽  
Shanshuo Zhu ◽  
Brigitte van de Cotte ◽  
...  
Keyword(s):  
Cell Wall ◽  
Root Growth ◽  
Growth Regulators ◽  
Growth Regulation ◽  
Phosphorylation Site ◽  
Primary Root ◽  
Root Tip ◽  
Arabidopsis Root ◽  
Growth Promoting ◽  
The Impact

Auxin plays a dual role in growth regulation and, depending on the tissue and concentration of the hormone, it can either promote or inhibit division and expansion processes in plants. Recent studies have revealed that, beyond transcriptional reprogramming, alternative auxin-controlled mechanisms regulate root growth. Here, we explored the impact of different concentrations of the synthetic auxin NAA that establish growth-promoting and -repressing conditions on the root tip proteome and phosphoproteome, generating a unique resource. From the phosphoproteome data, we pinpointed (novel) growth regulators, such as the RALF34-THE1 module. Our results, together with previously published studies, suggest that auxin, H+-ATPases, cell wall modifications and cell wall sensing receptor-like kinases are tightly embedded in a pathway regulating cell elongation. Furthermore, our study assigned a novel role to MKK2 as a regulator of primary root growth and a (potential) regulator of auxin biosynthesis and signalling, and suggests the importance of the MKK2 Thr31 phosphorylation site for growth regulation in the Arabidopsis root tip.

scholarly journals The steroid hormone 20-hydroxyecdysone counteracts insulin signaling via insulin receptor dephosphorylation

2021 ◽  
Vol 296 ◽  
pp. 100318
Author(s):  
Yan-Li Li ◽  
You-Xiang Yao ◽  
Yu-Meng Zhao ◽  
Yu-Qin Di ◽  
Xiao-Fan Zhao
Keyword(s):  
Insulin Receptor ◽  
Insulin Signaling ◽  
Steroid Hormone

Comprehensive Review on Neuro-Degenerative Type 3DM

2021 ◽  
Vol 18 ◽  
Author(s):  
Chandani V. Chandarana ◽  
Salona Roy
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Signaling ◽  
Insulin Signalling ◽  
Amyloid Β ◽  
Diabetes Mellitus Type 1 ◽  
Current Data ◽  
The Body ◽  
Type I ◽  
Therapeutic Benefits

: Alzheimer disease (AD) is thought to be the metabolic illness raised by defective insulin signaling, insulin resistance, and low insulin levels in the brain, according to a growing body of research. The "Type 3 diabetes" has been postulated for AD because reduced insulin signalling has molecular and physiological consequences that are comparable to Type I and Type 2 diabetes mellitus (Type 1 DM and Type 2 DM, respectively). The similarities between type 2 diabetes and Alzheimer's disease suggest that these clinical trials might yield therapeutic benefits. However, it's important to note that lowering your risk of Alzheimer's dementia, whether you have diabetes or not, is still a multidimensional process involving factors like exercise, smoking, alcohol, food, and mental challenge. The current aim is to show the relationship between T3D and AD being based on both the processing of amyloid-β (Aβ) precursor protein toxicity and the clearance of Aβ are the result of an impaired insulin signaling. The brain's metabolism with its high lipid content and energy needs, places excess demands on mitochondria and appears more susceptible to oxidative damage than the rest of the body. Current data suggests that increased oxidative stress relates to amyloid-β (Aβ) pathology and onset of AD.

scholarly journals A Complex Relationship between Immunity and Metabolism inDrosophilaDiet-Induced Insulin Resistance

2017 ◽  
Vol 38 (2) ◽  
Author(s):  
Laura Palanker Musselman ◽  
Jill L. Fink ◽  
Ana R. Grant ◽  
Jared A. Gatto ◽  
Bryon F. Tuthill ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Innate Immunity ◽  
Differential Expression ◽  
Insulin Signaling ◽  
Drug Targets ◽  
Fat Body ◽  
Dependent Manner ◽  
Content Type ◽  
Insulin Resistant ◽  
Fat Bodies

ABSTRACTBoth systemic insulin resistance and tissue-specific insulin resistance have been described inDrosophilaand are accompanied by many indicators of metabolic disease. The downstream mediators of insulin-resistant pathophysiology remain unclear. We analyzed insulin signaling in the fat body studying loss and gain of function. When expression of the soleDrosophilainsulin receptor (InR) was reduced in larval fat bodies, animals exhibited developmental delay and reduced size in a diet-dependent manner. Fat body InR knockdown also led to reduced survival on high-sugar diets. To look downstream of InR at potential mediators of insulin resistance, transcriptome sequencing (RNA-seq) studies in insulin-resistant fat bodies revealed differential expression of genes, including those involved in innate immunity. Obesity-associated insulin resistance led to increased susceptibility of flies to infection, as in humans. Reduced innate immunity was dependent on fat body InR expression. The peptidoglycan recognition proteins (PGRPs) PGRP-SB2 and PGRP-SC2 were selected for further study based on differential expression studies. Downregulating PGRP-SB2 selectively in the fat body protected animals from the deleterious effects of overnutrition, whereas downregulating PGRP-SC2 produced InR-like phenotypes. These studies extend earlier work linking the immune and insulin signaling pathways and identify new targets of insulin signaling that could serve as potential drug targets to treat type 2 diabetes.

scholarly journals Insulin Signaling, Lifespan and Stress Resistance Are Modulated by Metabotropic GABA Receptors on Insulin Producing Cells in the Brain of Drosophila

PLoS ONE ◽  
2010 ◽  
Vol 5 (12) ◽  
pp. e15780 ◽  
Author(s):  
Lina E. Enell ◽  
Neval Kapan ◽  
Jeannette A. E. Söderberg ◽  
Lily Kahsai ◽  
Dick R. Nässel
Keyword(s):  
Insulin Signaling ◽  
Stress Resistance ◽  
Gaba Receptors ◽  
Insulin Producing Cells ◽  
The Brain

A possible relationship between serum transferrin, growth hormone secretion and height velocity in children

1980 ◽  
Vol 93 (2) ◽  
pp. 134-138 ◽  
Author(s):  
M. Donnadieu ◽  
R. M. Schimpff ◽  
P. Garnier ◽  
J. L. Chaussain ◽  
J. C. Job
Keyword(s):  
Growth Hormone ◽  
Growth Regulation ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Height Velocity ◽  
Obese Children ◽  
Gh Secretion ◽  
Growth Promoting

Abstract. Since transferrin (Tf) in vitro has a growth-promoting activity and is associated with NSILA properties, the aim of this work was to study in vivo the relationships between Tf, somatomedin activity (SM), growth hormone (GH) secretion, and height velocity in children. An iv infusion of ornithine hydrochloride was given to 23 controls; the induced rise of GH was accompanied by a simultaneous fall of SM (r = −0.711, P < 0.001) and was preceded by a fall of Tf (r = −0.610, P < 0.01). In 17 obese children SM was within the normal range, when Tf levels were higher and arginineinduced GH peaks lower than in the controls, and a negative correlation was found between Tf basal levels and GH peaks (r = −0.608, P < 0.01). In 9 children with confirmed hypopituitarism the Tf levels were significantly lower than in the controls. In 14 children with confirmed or suspected hypopituitarism a single im injection of hGH (6 mg) failed to induce Tf variations over 24 h. In 39 of these children the height velocity was significantly correlated with Tf basal levels (r = 0.701, P < 0.001). These data suggest that transferrin is involved in growth regulation, and that GH secretion is related to transferrin levels by a feed-back mechanism.

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