scholarly journals The Difference δ-Cells Make in Glucose Control

Physiology ◽  
2018 ◽  
Vol 33 (6) ◽  
pp. 403-411 ◽  
Author(s):  
Mark O. Huising ◽  
Talitha van der Meulen ◽  
Jessica L. Huang ◽  
Mohammad S. Pourhosseinzadeh ◽  
Glyn M. Noguchi
Keyword(s):  
Glucose Control ◽  
Feedback Loop ◽  
Physiological Role ◽  
Glucagon Secretion ◽  
Negative Feedback Loop ◽  
Β Cells ◽  
Insulin And Glucagon Secretion ◽  
The Difference ◽  
Delta Cells

The role of beta and α-cells to glucose control are established, but the physiological role of δ-cells is poorly understood. Delta-cells are ideally positioned within pancreatic islets to modulate insulin and glucagon secretion at their source. We review the evidence for a negative feedback loop between delta and β-cells that determines the blood glucose set point and suggest that local δ-cell-mediated feedback stabilizes glycemic control.

Impaired glucagon secretory responses in mice lacking the type 1 sulfonylurea receptor

2005 ◽  
Vol 289 (4) ◽  
pp. E570-E577 ◽  
Author(s):  
Chiyo Shiota ◽  
Jonathan V. Rocheleau ◽  
Masakazu Shiota ◽  
David W. Piston ◽  
Mark A. Magnuson
Keyword(s):  
Glucose Concentration ◽  
Physiological Role ◽  
Glucagon Secretion ◽  
Sulfonylurea Receptor ◽  
Wild Type ◽  
Β Cells ◽  
Pancreas Perfusion ◽  
Perfusion Studies

Pancreatic α-cells, like β-cells, express ATP-sensitive K+ (KATP) channels. To determine the physiological role of KATP channels in α-cells, we examined glucagon secretion in mice lacking the type 1 sulfonylurea receptor ( Sur1). Plasma glucagon levels, which were increased in wild-type mice after an overnight fast, did not change in Sur1 null mice. Pancreas perfusion studies showed that Sur1 null pancreata lacked glucagon secretory responses to hypoglycemia and to synergistic stimulation by arginine. Pancreatic α-cells isolated from wild-type animals exhibited oscillations of intracellular free Ca2+ concentration ([Ca2+]i) in the absence of glucose that became quiescent when the glucose concentration was increased. In contrast, Sur1 null α-cells showed continuous oscillations in [Ca2+]i regardless of the glucose concentration. These findings indicate that KATP channels in α-cells play a key role in regulating glucagon secretion, thereby adding to the paradox of how mice that lack KATP channels maintain euglycemia.

scholarly journals Smad2/3 Activation Regulates Smad1/5/8 Signaling via a Negative Feedback Loop to Inhibit 3T3-L1 Adipogenesis

2021 ◽  
Vol 22 (16) ◽  
pp. 8472
Author(s):  
Senem Aykul ◽  
Jordan Maust ◽  
Vijayalakshmi Thamilselvan ◽  
Monique Floer ◽  
Erik Martinez-Hackert
Keyword(s):  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Adipose Tissues ◽  
Family Growth ◽  
Simultaneous Activation ◽  
Adipocyte Hypertrophy ◽  
Adipocyte Development ◽  
Energy Surplus

Adipose tissues (AT) expand in response to energy surplus through adipocyte hypertrophy and hyperplasia. The latter, also known as adipogenesis, is a process by which multipotent precursors differentiate to form mature adipocytes. This process is directed by developmental cues that include members of the TGF-β family. Our goal here was to elucidate, using the 3T3-L1 adipogenesis model, how TGF-β family growth factors and inhibitors regulate adipocyte development. We show that ligands of the Activin and TGF-β families, several ligand traps, and the SMAD1/5/8 signaling inhibitor LDN-193189 profoundly suppressed 3T3-L1 adipogenesis. Strikingly, anti-adipogenic traps and ligands engaged the same mechanism of action involving the simultaneous activation of SMAD2/3 and inhibition of SMAD1/5/8 signaling. This effect was rescued by the SMAD2/3 signaling inhibitor SB-431542. By contrast, although LDN-193189 also suppressed SMAD1/5/8 signaling and adipogenesis, its effect could not be rescued by SB-431542. Collectively, these findings reveal the fundamental role of SMAD1/5/8 for 3T3-L1 adipogenesis, and potentially identify a negative feedback loop that links SMAD2/3 activation with SMAD1/5/8 inhibition in adipogenic precursors.

The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development

Development ◽  
1998 ◽  
Vol 125 (22) ◽  
pp. 4417-4425 ◽  
Author(s):  
M. Takahashi ◽  
K. Tamura ◽  
D. Buscher ◽  
H. Masuya ◽  
S. Yonei-Tamura ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Limb Development ◽  
Feedback Loop ◽  
Limb Bud ◽  
Negative Regulator ◽  
Negative Feedback Loop ◽  
Vertebrate Limb ◽  
Limb Outgrowth ◽  
Vertebrate Limb Development

We have determined that Strong's Luxoid (lstJ) [corrected] mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in lstJ [corrected] mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.

scholarly journals Activities and some properties of 5′-nucleotidase, adenosine kinase and adenosine deaminase in tissues from vertebrates and invertebrates in relation to the control of the concentration and the physiological role of adenosine

1978 ◽  
Vol 174 (3) ◽  
pp. 965-977 ◽  
Author(s):  
J R S Arch ◽  
E A Newsholme
Keyword(s):  
Adenosine Deaminase ◽  
Physiological Role ◽  
Adenosine Kinase ◽  
British Library ◽  
Adenosine Concentration ◽  
Effects Of Ph ◽  
The Difference ◽  
Low Activity

1. The maximal activities of 5′-nucleotidase, adenosine kinase and adenosine deaminase together with the Km values for their respective substrates were measured in muscle, nervous tissue and liver from a large range of animals to provide information on the mechanism of control of adenosine concentration in the tissues. 2. Detailed evidence that the methods used were optimal for the extraction and assay of these enzymes has been deposited as Supplementary Publication SUP 50088 (16pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K.,from whom copies can be obtained on the terms indicated in Biochem. J. (1978), 169, 5. This evidence includes the effects of pH and temperature on the activities of the enzymes. 3. In many tissues, the activities of 5′-nucleotidase were considerably higher than the sum of the activities of adenosine kinase and deaminase, which suggests that the activity of the nucleotidase must be markedly inhibited in vivo so that adenosine does not accumulate. In the tissues in which comparison is possible, the Km of the nucleotidase is higher than the AMP content of the tissue, and since some of the latter may be bound within the cell, the low concentration of substrate may, in part, be responsible for a low activity in vivo. 4. In most tissues and animals investigated, the values of the Km of adenosine kinase for adenosine are between one and two orders of magnitude lower than those for the deaminase. It is suggested that 5′-nucleotidase and adenosine kinase are simultaneously active so that a substrate cycle between AMP and adenosine is produced: the difference in Km values between kinase and deaminase indicates that, via the cycle, small changes in activity of kinase or nucleotidase produce large changes in adenosine concentration. 5. The activities of adenosine kinase or deaminase from vertebrate muscles are inversely correlated with the activities of phosphorylase in these muscles. Since the magnitude of the latter activities are indicative of the anaerobic nature of muscles, this negative correlation supports the hypothesis that an important role of adenosine is the regulation of blood flow in the aerobic muscles.

scholarly journals Arginine-induced pancreatic hormone secretion during exercise in rats

1996 ◽  
Vol 81 (6) ◽  
pp. 2528-2533 ◽  
Author(s):  
Fethi Trabelsi ◽  
Jean-Marc Lavoie
Keyword(s):  
Hormone Secretion ◽  
Exercise Bout ◽  
Glucagon Secretion ◽  
Sympathoadrenal System ◽  
Control Groups ◽  
Insulin And Glucagon Secretion ◽  
Hormone Responses ◽  
Pancreatic Hormone ◽  
Hepatic Branch

Trabelsi, Fethi, and Jean-Marc Lavoie. Arginine-induced pancreatic hormone secretion during exercise in rats. J. Appl. Physiol. 81(6): 2528–2533, 1996.—The aim of the present investigation was to 1) determine whether arginine-induced pancreatic hormone secretion can be modified during an exercise bout, and 2) verify whether the sectioning of the hepatic branch of the vagus nerve can alter the arginine-induced insulin and glucagon secretion during exercise in rats. To this end, we studied the effects of an intraperitoneal injection of arginine (1 g/kg body mass) during an exercise bout (30 min, 26 m/min, 0% grade) on the pancreatic hormone responses. These effects were determined in one group of sham-operated exercising rats and compared with three control groups: one group of resting rats, one group of saline-injected exercising rats, and one group of hepatic-vagotomized exercising rats. Five minutes after the injection of arginine, significant ( P < 0.05) increases in insulin, glucagon, and C-peptide concentrations were observed in exercising as well as in resting rats. These responses were not, however, altered by the hepatic vagotomy and/or by the exercise bout. It is concluded that arginine is a potent stimulus of pancreatic hormone secretion during exercise, even though the sympathoadrenal system is activated. These results also indicate that a hepatic vagotomy does not seem to influence arginine-induced hormonal pancreatic responses and question the role of the putative hepatic arginoreceptors in the control of the pancreatic hormone secretion during exercise.

scholarly journals Salt-Inducible Kinase 1 Terminates cAMP Signaling by an Evolutionarily Conserved Negative-Feedback Loop in β-Cells

Diabetes ◽  
2015 ◽  
Vol 64 (9) ◽  
pp. 3189-3202 ◽  
Author(s):  
Min-Jung Kim ◽  
Su-Kyung Park ◽  
Ji-Hyun Lee ◽  
Chang-Yun Jung ◽  
Dong Jun Sung ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Feedback Loop ◽  
Camp Signaling ◽  
Negative Feedback Loop ◽  
Β Cells ◽  
Evolutionarily Conserved

Downstream regulatory element antagonistic modulator regulates islet prodynorphin expression

2006 ◽  
Vol 291 (3) ◽  
pp. E587-E595 ◽  
Author(s):  
David A. Jacobson ◽  
Julie Cho ◽  
Luis R. Landa ◽  
Natalia A. Tamarina ◽  
Michael W. Roe ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Regulatory Element ◽  
Glucagon Secretion ◽  
Dependent Manner ◽  
Β Cells ◽  
Dynorphin A ◽  
Calcium Dependent ◽  
Low Glucose ◽  
Stimulation Of

Calcium-binding proteins regulate transcription and secretion of pancreatic islet hormones. Here, we demonstrate neuroendocrine expression of the calcium-binding downstream regulatory element antagonistic modulator (DREAM) and its role in glucose-dependent regulation of prodynorphin (PDN) expression. DREAM is distributed throughout β- and α-cells in both the nucleus and cytoplasm. As DREAM regulates neuronal dynorphin expression, we determined whether this pathway is affected in DREAM−/− islets. Under low glucose conditions, with intracellular calcium concentrations of <100 nM, DREAM−/− islets had an 80% increase in PDN message compared with controls. Accordingly, DREAM interacts with the PDN promoter downstream regulatory element (DRE) under low calcium (<100 nM) conditions, inhibiting PDN transcription in β-cells. Furthermore, β-cells treated with high glucose (20 mM) show increased cytoplasmic calcium (∼200 nM), which eliminates DREAM's interaction with the DRE, causing increased PDN promoter activity. As PDN is cleaved into dynorphin peptides, which stimulate κ-opioid receptors expressed predominantly in α-cells of the islet, we determined the role of dynorphin A-(1–17) in glucagon secretion from the α-cell. Stimulation with dynorphin A-(1–17) caused α-cell calcium fluctuations and a significant increase in glucagon release. DREAM−/− islets also show elevated glucagon secretion in low glucose compared with controls. These results demonstrate that PDN transcription is regulated by DREAM in a calcium-dependent manner and suggest a role for dynorphin regulation of α-cell glucagon secretion. The data provide a molecular basis for opiate stimulation of glucagon secretion first observed over 25 years ago.

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