PACAP stimulates insulin secretion by PAC1 receptor and ion channels in β-cells

Liu, Mengmeng; Yang, Xiaohua; Bai, Tao; Liu, Zhihong; Liu, Tao; Wang, Yan; Liu, Yunfeng; Zhang, Yi

doi:10.1016/j.cellsig.2019.05.006

Cited by 14 publications

(17 citation statements)

References 36 publications

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“…Both subtypes elevate insulin secretion on isolated islets and perfused pancreas, where the stimulating potential of PACAP27 and PACAP38 is equal (Fridolf et al 1992;Klinteberg et al 1996;Yada et al 1994). It has been shown 1 3 that PACAP38 stimulates insulin secretion glucose-and dose-dependently via the PAC1 receptor, not by VPAC1 or VPAC2 receptors (Liu et al 2019). It has also been proven that PAC1 and VPAC2 receptor deletion can cause glucose intolerance, influencing mediation of prandial insulin secretion and glucagon response to hypoglycaemia (Winzell and Ahrén 2007).…”

Section: Introductionmentioning

confidence: 99%

PACAP and PAC1 Receptor Expression in Human Insulinomas

Ferencz

Tóth

Kaszás

et al. 2021

Int J Pept Res Ther

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with widespread occurrence and diverse functions. PACAP binds to specific PAC1 and non-specific VPAC1/2 receptors. PACAP is considered as a growth factor, as it plays important roles during development and participates in reparative processes. Highest concentrations are found in the nervous system and endocrine glands, where several functions are known, including actions in tissue growth, differentiation and tumour development. Therefore, we have investigated expression of PACAP and its receptors in different tumours, including those of endocrine glands. We showed earlier that PACAP and PAC1 receptor staining intensity decreased in pancreatic ductal adenocarcinoma. In the present study we aimed to investigate alterations of PACAP and PAC1 receptor in human insulinoma and compared the immunostaining pattern with samples from chronic pancreatitis patients. We collected perioperative and histological data of patients who underwent operation because of insulinoma or chronic pancreatitis over a five-year-long period. Histology showed chronic pancreatitis with severe scar formation in pancreatitis patients, while tumour samples evidenced Grade 1 or 2 insulinoma. PACAP and PAC1 receptor expression was studied using immunohistochemistry. Staining intensity was very strong in the Langerhans islets of normal tissue and discernible staining was also observed in the exocrine pancreas. Immunostaining intensity for both PACAP and PAC1 receptor was markedly weaker in insulinoma samples, and disappeared from chronic pancreatitis samples except for intact islets. These findings show that PAC1 receptor/PACAP signalling is altered in insulinoma and this suggests a possible involvement of this system in tumour growth or differentiation.

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Section: Introductionmentioning

confidence: 99%

PACAP and PAC1 Receptor Expression in Human Insulinomas

Ferencz

Tóth

Kaszás

et al. 2021

Int J Pept Res Ther

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“…This observation is in accordance with our previous results studying the effects of PACAP treatment in diabetic nephropathy [ 38 ]. These data suggest that PACAP, in spite of its effects on glucose homeostasis and insulin secretion [ 53 , 54 ], is protective in our diabetic neuropathy model, not by acting directly on glucose levels, but most probably due to its neuro- and general cytoprotective effects [ 20 , 79 ]. Although, as outlined above, PACAP is known to stimulate insulin secretion, it did not alter blood glucose levels in this model of type I diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Diabetic neuropathy is a common microvascular complication of diabetes, affecting around 50–70% of diabetic patients [ 51 , 52 ]. PACAP is involved in glucose metabolism and insulin secretion [ 53 , 54 ], in addition to protective effects exerted on the insulin-producing pancreatic beta cells [ 55 , 56 ]. More importantly, from a neuropathy point of view, PACAP influences Schwann cell functions [ 57 , 58 ], stimulates axonal growth [ 59 , 60 ], and promotes regeneration of peripheral nerves [ 61 , 62 , 63 , 64 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of PACAP in a Rat Model of Diabetic Neuropathy

Kiss

Bánki

Gaszner

et al. 2021

IJMS

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Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide with a widespread occurrence and diverse effects. PACAP has well-documented neuro- and cytoprotective effects, proven in numerous studies. Among others, PACAP is protective in models of diabetes-associated diseases, such as diabetic nephropathy and retinopathy. As the neuropeptide has strong neurotrophic and neuroprotective actions, we aimed at investigating the effects of PACAP in a rat model of streptozotocin-induced diabetic neuropathy, another common complication of diabetes. Rats were treated with PACAP1-38 every second day for 8 weeks starting simultaneously with the streptozotocin injection. Nerve fiber morphology was examined with electron microscopy, chronic neuronal activation in pain processing centers was studied with FosB immunohistochemistry, and functionality was assessed by determining the mechanical nociceptive threshold. PACAP treatment did not alter body weight or blood glucose levels during the 8-week observation period. However, PACAP attenuated the mechanical hyperalgesia, compared to vehicle-treated diabetic animals, and it markedly reduced the morphological signs characteristic for neuropathy: axon–myelin separation, mitochondrial fission, unmyelinated fiber atrophy, and basement membrane thickening of endoneurial vessels. Furthermore, PACAP attenuated the increase in FosB immunoreactivity in the dorsal spinal horn and periaqueductal grey matter. Our results show that PACAP is a promising therapeutic agent in diabetes-associated complications, including diabetic neuropathy.

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“…Cells treated with different concentrations of LB. The supernatants were collected from each well, and secreted insulin in which was determined using the Iodine [ 125 I]− Insulin Radioimmunoassay Kit (North Biological Technology Research Institute of Beijing) according to the manufacturer's instructions 25 . The experiment was repeated 3 times.…”

Section: Methodsmentioning

confidence: 99%

Loureirin B activates GLP‐1R and promotes insulin secretion in Ins‐1 cells

Ding

Xia

Zhang

et al. 2020

J Cellular Molecular Medi

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Diabetes mellitus (DM), as a kind of metabolic disease, is characterized by the deficiency of insulin function and secretion, which leads to chronic hyperglycaemia, affecting the metabolism of protein, fat and carbohydrate. 1,2 DM patients mainly manifested as polyphagia, polydipsia, polyuria and weight loss. Type 2 diabetes mellitus (T2DM) accounts for 90-95% of diabetic patients. Insulin resistance and β cell failure (decrease of β cell quality, glucose sensitivity and secretion ability) are the main characteristics. 3,4 DM is regarded by the World Health Organization (WHO) as one of the four main non-communicable diseases (NCDs). 5 Current treatment options for DM include the sole application of exogenous insulin or combining it with allopathic drugs. Those hypoglycaemic drugs decrease fasting blood glucose through many pathways, such as biguanides (metformin), sulphonylureas (glibenclamide) and alpha-glucosidase inhibitors (acarbose and miglitol). 6 Many efforts have been made to explore safe and effective anti-T2DM drugs. 7 Glucagon-like peptide-1 (GLP-1) is a glucose-dependent hormone that stimulates islet beta cells to secrete insulin in a glucose-dependent manner. 8 GLP-1 receptor (GLP-1R) belongs to the glucagon receptor B family and distributes in pancreatic cells, gastrointestinal tract, cardiovascular, lung and central nervous system. 9 GLP-1 continues to activate the GLP-1R, which increases insulin secretion, beta-cell proliferation and regeneration. 10,11 GLP-1R is an important target for insulin secretion, the agonists of which are widely used in the treatment of DM. 12 A series of GLP-1R agonists, such as exdin-4, liraglutide and lixisenatide, have been developed. 13,14 In addition to significantly reducing blood glucose, GLP-1R agonists can also reduce weight, blood pressure, improving the function of β cell, which showed the potential to delay the progress of diabetes and reduce cardiovascular complications. 13 GLP-1R agonists can delay intestinal

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PACAP stimulates insulin secretion by PAC1 receptor and ion channels in β-cells

Cited by 14 publications

References 36 publications

PACAP and PAC1 Receptor Expression in Human Insulinomas

PACAP and PAC1 Receptor Expression in Human Insulinomas

Protective Effects of PACAP in a Rat Model of Diabetic Neuropathy

Loureirin B activates GLP‐1R and promotes insulin secretion in Ins‐1 cells

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