| Title |
CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion
|
|---|---|
| Published in |
Diabetologia, June 2016
|
| DOI | 10.1007/s00125-016-4020-6 |
| Pubmed ID | |
| Authors |
Mia Abels, Matteo Riva, Hedvig Bennet, Emma Ahlqvist, Oleg Dyachok, Vini Nagaraj, Liliya Shcherbina, Rikard G. Fred, Wenny Poon, Maria Sörhede-Winzell, Joao Fadista, Andreas Lindqvist, Lena Kask, Ramasri Sathanoori, Marloes Dekker-Nitert, Michael J. Kuhar, Bo Ahrén, Claes B. Wollheim, Ola Hansson, Anders Tengholm, Malin Fex, Erik Renström, Leif Groop, Valeriya Lyssenko, Nils Wierup |
| Abstract |
Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart (-/-) mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affects insulin and glucagon secretion in vitro in humans and in vivo in mice. CART expression was assessed in human type 2 diabetic and non-diabetic control pancreases and rodent models of diabetes. Insulin and glucagon secretion was examined in isolated islets and in vivo in mice. Ca(2+) oscillation patterns and exocytosis were studied in mouse islets. We report an important role of CART in human islet function and glucose homeostasis in mice. CART was found to be expressed in human alpha and beta cells and in a subpopulation of mouse beta cells. Notably, CART expression was several fold higher in islets of type 2 diabetic humans and rodents. CART increased insulin secretion in vivo in mice and in human and mouse islets. Furthermore, CART increased beta cell exocytosis, altered the glucose-induced Ca(2+) signalling pattern in mouse islets from fast to slow oscillations and improved synchronisation of the oscillations between different islet regions. Finally, CART reduced glucagon secretion in human and mouse islets, as well as in vivo in mice via diminished alpha cell exocytosis. We conclude that CART is a regulator of glucose homeostasis and could play an important role in the pathophysiology of type 2 diabetes. Based on the ability of CART to increase insulin secretion and reduce glucagon secretion, CART-based agents could be a therapeutic modality in type 2 diabetes. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Switzerland | 1 | 17% |
| Mexico | 1 | 17% |
| Brazil | 1 | 17% |
| Unknown | 3 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 67% |
| Scientists | 1 | 17% |
| Science communicators (journalists, bloggers, editors) | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 3% |
| Unknown | 36 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 9 | 24% |
| Researcher | 7 | 19% |
| Student > Ph. D. Student | 5 | 14% |
| Other | 3 | 8% |
| Student > Master | 3 | 8% |
| Other | 8 | 22% |
| Unknown | 2 | 5% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 27% |
| Biochemistry, Genetics and Molecular Biology | 8 | 22% |
| Agricultural and Biological Sciences | 6 | 16% |
| Nursing and Health Professions | 3 | 8% |
| Neuroscience | 3 | 8% |
| Other | 4 | 11% |
| Unknown | 3 | 8% |
Attention Score in Context
This research output has an Altmetric Attention Score of 77. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 April 2023.
All research outputs
#528,347
of 24,614,554 outputs
Outputs from Diabetologia
#275
of 5,282 outputs
Outputs of similar age
#10,868
of 359,800 outputs
Outputs of similar age from Diabetologia
#12
of 85 outputs
Altmetric has tracked 24,614,554 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,282 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 24.3. This one has done particularly well, scoring higher than 94% of its peers.
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We're also able to compare this research output to 85 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.