Intraperitoneal PACAP Administration Decreases Blood Glucose in GK Rats, and in Normal and High Fat Diet Mice

Yada, T.; Sakurada, Masaya; Filipsson, Karin; Kikuchi, Masatoshi; Åhrén, Bo

doi:10.1111/j.1749-6632.2000.tb06974.x

Cited by 44 publications

(25 citation statements)

References 12 publications

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“…For example, daily PACAP injection in high-fat diet-induced obesity or GotoKakizaki rats enhanced glucose tolerance and reduced circulating glucose levels (Yada et al 2000). However, PACAP-mediated epinephrine secretion and plasma glucagon levels may worsen prognosis of T2D instead of improving it.…”

Section: Glucagon Receptor Antagonists and Vpac2 Selective Agonists Fmentioning

confidence: 99%

Therapeutic potential of VIP vs PACAP in diabetes

Şanlioğlu

Karaçay²,

Balcı³

et al. 2012

Journal of Molecular Endocrinology

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Type 2 diabetes (T2D) is characterized by chronic insulin resistance and a progressive decline in beta-cell function. Although rigorous glucose control can reduce morbidity and mortality associated with diabetes, achieving optimal longterm glycemic control remains to be accomplished in many diabetic patients. As beta-cell mass and function inevitably decline in T2D, exogenous insulin administration is almost unavoidable as a final outcome despite the use of oral antihyperglycemic agents in many diabetic patients. Pancreatic islet cell death, but not the defect in new islet formation or beta-cell replication, has been blamed for the decrease in beta-cell mass observed in T2D patients. Thus, therapeutic approaches designed to protect islet cells from apoptosis could significantly improve the management of T2D, because of its potential to reverse diabetes not just ameliorate glycemia. Therefore, an ideal beta-cell-preserving agent is expected to protect beta cells from apoptosis and stimulate postprandial insulin secretion along with increasing beta-cell replication and/or islet neogenesis. One such potential agent, the islet endocrine neuropeptide vasoactive intestinal peptide (VIP) strongly stimulates postprandial insulin secretion. Because of its broad spectrum of biological functions such as acting as a potent anti-inflammatory factor through suppression of Th1 immune response, and induction of immune tolerance via regulatory T cells, VIP has emerged as a promising therapeutic agent for the treatment of many autoimmune diseases including diabetes.

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Section: Glucagon Receptor Antagonists and Vpac2 Selective Agonists Fmentioning

confidence: 99%

Therapeutic potential of VIP vs PACAP in diabetes

Şanlioğlu

Karaçay²,

Balcı³

et al. 2012

Journal of Molecular Endocrinology

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“…PACAP has been shown to reduce the hyperglycemia in rodent diabetes (high fat-fed mice and GK rats) (31). However, one problem is that PACAP stimulates glucagon secretion and the peptide has potent vasoactive effects, which would limit its usefulness in treatment.…”

Section: Parasympathetic Nervous Systemmentioning

confidence: 99%

Neuropeptides and the Regulation of Islet Function

2006

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The pancreatic islets are richly innervated by autonomic nerves. The islet parasympathetic nerves emanate from intrapancreatic ganglia, which are controlled by preganglionic vagal nerves. The islet sympathetic nerves are postganglionic with the nerve cell bodies located in ganglia outside the pancreas. The sensory nerves originate from dorsal root ganglia near the spinal cord. Inside the islets, nerve terminals run close to the endocrine cells. In addition to the classic neurotransmitters acetylcholine and norepinephrine, several neuropeptides exist in the islet nerve terminals. These neuropeptides are vasoactive intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide, gastrin-releasing polypeptide, and cocaineand amphetamine-regulated transcript in parasympathetic nerves; neuropeptide Y and galanin in the sympathetic nerves; and calcitonin gene-related polypeptide in sensory nerves. Activation of the parasympathetic nerves and administration of their neurotransmitters stimulate insulin and glucagon secretion, whereas activation of the sympathetic nerves and administration of their neurotransmitters inhibit insulin but stimulate glucagon secretion. The autonomic nerves contribute to the cephalic phase of insulin secretion, to glucagon secretion during hypoglycemia, to pancreatic polypeptide secretion, and to the inhibition of insulin secretion, which is seen during stress. In rodent models of diabetes, the number of islet autonomic nerves is upregulated. This review focuses on neural regulation of islet function, with emphasis on the neuropeptides. Diabetes 55 (Suppl. 2):S98 -S107, 2006 S ince the discovery of nerves in the pancreatic islet by Paul Langerhans in his thesis from 1869, the neural-islet axis has been explored by a number of neuroanatomists, physiologists, and endocrinologists (rev. in 1-3). It is currently known that branches of the parasympathetic and sympathetic as well as the sensory nervous system innervate the islets with nerve terminals ending closely to the islet endocrine cells. It is also known that these nerves affect islet hormone secretion. The classic neurotransmitters in the islet autonomic nerves are acetylcholine and norepinephrine. During the last decades, the contribution to neural regulation of islet function also by neuropeptides has been established (rev. in 4). Several neuropeptides are localized to islet nerve terminals, are released from the pancreatic nerves upon nerve stimulation, and influence islet hormone secretion. It is also known that the islet innervation is altered in animal models of type 2 diabetes (5). The autonomic nervous system has also been suggested to be involved in the regulation of islet mass (6). The present review highlights the role of neuropeptides in islet function. PARASYMPATHETIC NERVOUS SYSTEMAnatomy and effects. The parasympathetic nerves innervating the pancreatic islets emanate from the pancreatic ganglia, which are innervated by preganglionic parasympathetic nerves originating in the dorsal motor nucleus of the vagus. Activ...

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“…The potential contribution of prevention of PACAP inactivation by DPP-4 inhibition for the glucose-lowering action of treatment remains to be studied in more detail since PACAP, besides stimulating insulin secretion, also stimulates, and does not inhibit, glucagon secretion (43). Nevertheless, long-term administration of PACAP in animal models of diabetes has been shown to improve glycemia (47).…”

Section: Prevention Of Inactivation Of Other Biologically Active Peptmentioning

confidence: 99%

Pleiotropic Mechanisms for the Glucose-Lowering Action of DPP-4 Inhibitors

2014

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DPP-4 is an enzyme that is widely expressed throughout the body and abundantly expressed in endothelial cells. It is attached to the intravascular portion of vascular endothelial cells and also exists in a soluble circulating form (4). It is a serine protease that cleaves peptides between the amino acid 2 and 3 from the N-terminal end, particularly if the second amino acid is alanine or proline. GLP-1 has alanine as the second amino acid and is therefore a substrate for DPP-4, which cleaves the intact GLP-1 7-36 to GLP-1 9-36 , which is largely inactive. The

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Intraperitoneal PACAP Administration Decreases Blood Glucose in GK Rats, and in Normal and High Fat Diet Mice

Cited by 44 publications

References 12 publications

Therapeutic potential of VIP vs PACAP in diabetes

Therapeutic potential of VIP vs PACAP in diabetes

Neuropeptides and the Regulation of Islet Function

Pleiotropic Mechanisms for the Glucose-Lowering Action of DPP-4 Inhibitors

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