Increased expression of adenylyl cyclase 3 in pancreatic islets and central nervous system of diabetic Goto-Kakizaki rats

Ahmed, Muthanna J.; Kovoor, Abraham; Nordman, Sofia; Seman, Norhashimah Abu; Gu, Tianwei; Efendić, Suad; Brismar, Kerstin; Östenson, Claes‐Göran; Gu, Harvest F.

doi:10.4161/isl.22283

Cited by 19 publications

(23 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effects of hyperglycaemia may be aggravated by lowered PKA activity caused by increased expression of the PKA‐inhibiting peptide PKIβ . These results contrast to findings from diabetic GK rats, in which insulin secretion is reduced despite increased islet expression of several ACs, including AC3 and AC8 . It is possible that the altered cAMP metabolism in this model reflects compensation for other defects.…”

Section: Camp Signalling In Diabetescontrasting

confidence: 67%

“…Some of these ACs are also activated or inhibited by Ca 2+ /calmodulin and phosphorylation by protein kinases. The Ca 2+ ‐stimulated isoforms AC1, AC3 and AC8, as well as the Ca 2+ ‐insensitive AC9 have been found important in rodent β‐cells and insulinoma cells. Less is known about human β‐cells but the Ca 2+ ‐ and protein kinase A (PKA)‐inhibited AC5 was recently found critical for glucose stimulation of insulin secretion .…”

Section: Components Of the Camp Signalling Systemmentioning

confidence: 99%

See 1 more Smart Citation

cAMP signalling in insulin and glucagon secretion

Tengholm

Gylfe

2017

Diabetes Obesity Metabolism

193

130

View full text Add to dashboard Cite

The "second messenger" archetype cAMP is one of the most important cellular signalling molecules with central functions including the regulation of insulin and glucagon secretion from the pancreatic β-and α-cells, respectively. cAMP is generally considered as an amplifier of insulin secretion triggered by Ca 2+ elevation in the β-cells. Both messengers are also positive modulators of glucagon release from α-cells, but in this case cAMP may be the important regulator and Ca 2+ have a more permissive role. The actions of cAMP are mediated by protein kinase A (PKA) and the guanine nucleotide exchange factor Epac. The present review focuses on how cAMP is regulated by nutrients, hormones and neural factors in β-and α-cells via adenylyl cyclase-catalysed generation and phosphodiesterase-mediated degradation. We will also discuss how PKA and Epac affect ion fluxes and the secretory machinery to transduce the stimulatory effects on insulin and glucagon secretion. Finally, we will briefly describe disturbances of the cAMP system associated with diabetes and how cAMP signalling can be targeted to normalize hypo-and hypersecretion of insulin and glucagon, respectively, in diabetic patients. " cAMP is essential not only for neurohormonal amplification of insulin release but also for glucose-stimulated secretion. "As cAMP is generated in response to glucose (see below), the messenger has come into fashion again and must be considered not only when discussing neurohormonal amplification of insulin release but also when analysing glucose-stimulated secretion. There is even a

show abstract

Section: Camp Signalling In Diabetescontrasting

confidence: 67%

Section: Components Of the Camp Signalling Systemmentioning

confidence: 99%

cAMP signalling in insulin and glucagon secretion

Tengholm

Gylfe

2017

Diabetes Obesity Metabolism

193

130

View full text Add to dashboard Cite

show abstract

“…23 Mice carrying the AC3Jll mutant allele exhibit increased AC3 activity in response to forskolin and are protected from HFD-induced obesity. 24 In the present study, liraglutide upregulated the hepatic and serum AC3 levels.…”

Section: Discussionmentioning

confidence: 99%

Liraglutide reduces body weight by upregulation of adenylate cyclase 3

Liang

Xia

et al. 2017

Nutr. Diabetes

View full text Add to dashboard Cite

Objective:According to recent studies, adenylate cyclase 3 (AC3) is associated with obesity. Liraglutide reduces blood glucose levels and body weight (BW). We performed a 2 × 2 factorial experiment to study the relationships among AC3, liraglutide and obesity and to obtain a more comprehensive understanding of the mechanisms underlying the physiological effects of liraglutide on obesity.Methods:A high-fat diet was used to induce obesity in C57BL/6J mice. Both the normal and obese mice were treated with liraglutide (1 mg kg−1) or saline twice daily for 8 weeks. The hepatic levels of the AC3 and glucagon-like peptide receptor (GLP-1R) mRNAs and proteins were measured by quantitative real-time PCR and western blotting, respectively. The serum AC3 levels were detected using a rat/mouse AC3 enzyme-linked immunosorbent assay kit.Results:The administration of liraglutide significantly decreased the BW in obese mice and normal control mice. The BW of obese mice exhibited a more obvious decrease. Hepatic AC3 mRNA and protein levels and serum AC3 levels were significantly reduced in obese mice compared with those in normal control mice. The administration of liraglutide significantly increased the hepatic expression of the AC3 and GLP-1R mRNAs and proteins and serum AC3 levels. The hepatic expression of the AC3 mRNA and protein and serum AC3 levels were negatively correlated with BW loss in the liraglutide-treated group. Pearson’s correlation coefficients for these comparisons are r=−0.448, P=0.048; r=−0.478, P=0.046; and r=−0.909, P=0.000, respectively.Conclusions:Based on our research, liraglutide reduces BW, possibly by increasing the expression of AC3.

show abstract

“…ADCY3 encodes the membrane‐associated adenylyl cyclase 3 (ADCY3) protein, which catalyses the formation of cyclic 3′5′‐AMP (cAMP) from ATP . ADCY3 is widely expressed, and found in tissues, such as brain, pancreas, adipose and skeletal muscles; moreover, in animal models, ADCY3 has been found in specific regions of the brain, including hypothalamus .…”

Section: Genetic Association Studies Of Metabolic Traits In Isolated mentioning

confidence: 99%

Genetics of metabolic traits in Greenlanders: lessons from an isolated population

Andersen

Hansen

2018

J Intern Med

View full text Add to dashboard Cite

In this review, we describe the extraordinary population of Greenland, which differs from large outbred populations of Europe and Asia, both in terms of population history and living conditions. Many years in isolation, small population size and an extreme environment have shaped the genetic composition of the Greenlandic population. The unique genetic background combined with the transition from a traditional Inuit lifestyle and diet, to a more Westernized lifestyle, has led to an increase in the prevalence of metabolic conditions like obesity, where the prevalence from 1993 to 2010 has increased from 16.4% to 19.4% among men, and from 13.0% to 25.4% among women, type 2 diabetes and cardiovascular diseases. The genetic susceptibility to metabolic conditions has been explored in Greenlanders, as well as other isolated populations, taking advantage of population-genetic properties of these populations. During the last 10 years, these studies have provided examples of loci showing evidence of positive selection, due to adaption to Arctic climate and Inuit diet, including TBC1D4 and FADS/CPT1A, and have facilitated the discovery of several loci associated with metabolic phenotypes. Most recently, the c.2433-1G>A loss-of-function variant in ADCY3 associated with obesity and type 2 diabetes was described. This locus has provided novel biological insights, as it has been shown that reduced ADCY3 function causes obesity through disrupted function in primary cilia. Future studies of isolated populations will likely provide further genetic as well as biological insights.

show abstract

Increased expression of adenylyl cyclase 3 in pancreatic islets and central nervous system of diabetic Goto-Kakizaki rats

Cited by 19 publications

References 27 publications

cAMP signalling in insulin and glucagon secretion

cAMP signalling in insulin and glucagon secretion

Liraglutide reduces body weight by upregulation of adenylate cyclase 3

Genetics of metabolic traits in Greenlanders: lessons from an isolated population

Contact Info

Product

Resources

About