Dopamine-Mediated Autocrine Inhibitory Circuit Regulating Human Insulin Secretion in Vitro

Simpson, Norman R.; Maffei, Antonella; Freeby, Matthew; Burroughs, Steven; Freyberg, Zachary; Javitch, Jonathan A.; Leibel, Rudolph L.; Harris, Paul E.

doi:10.1210/me.2012-1101

Cited by 76 publications

(113 citation statements)

References 68 publications

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“…The other likely possibility is paracrine control of islet blood flow arising from products secreted from the islet cells. Three possible molecules that can control vasodilation (6,10,13,15,19,21,22,27,56) and are known to be associated with insulin secretion are nitric oxide (NO), ATP/adenosine, and dopamine (23,31,34,48,51,54). Because the control of islet blood velocity needs to occur upstream of the ␤-cells, paracrine control must also occur upstream.…”

Section: E328 Connexin 36 Mediates Blood Cell Flow In Isletsmentioning

confidence: 99%

“…This residual glucose-dependent velocity increase is due at least partially to central nervous system signaling (24) coupled with the potential paracrine signal from islet ␤-cells. Because the release of paracrine mediators likely corresponds to insulin secretion from the ␤-cells (23,31,34,48,51,54), we would expect differences in their temporal profile, although their total level may be unchanged as a function of Cx36 expression (18). Such a paracrine signal(s) would putatively control local blood cell velocity via transmission to arterioles immediately adjacent to islets.…”

Section: E328 Connexin 36 Mediates Blood Cell Flow In Isletsmentioning

confidence: 99%

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Connexin 36 mediates blood cell flow in mouse pancreatic islets

Short

Head

Piston

2014

American Journal of Physiology-Endocrinology and Metabolism

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The insulin-secreting β-cells are contained within islets of Langerhans, which are highly vascularized. Blood cell flow rates through islets are glucose-dependent, even though there are no changes in blood cell flow within in the surrounding exocrine pancreas. This suggests a specific mechanism of glucose-regulated blood flow in the islet. Pancreatic islets respond to elevated glucose with synchronous pulses of electrical activity and insulin secretion across all β-cells in the islet. Connexin 36 (Cx36) gap junctions between islet β-cells mediate this synchronization, which is lost in Cx36 knockout mice (Cx36−/−). This leads to glucose intolerance in these mice, despite normal plasma insulin levels and insulin sensitivity. Thus, we sought to investigate whether the glucose-dependent changes in intraislet blood cell flow are also dependent on coordinated pulsatile electrical activity. We visualized and quantified blood cell flow using high-speed in vivo fluorescence imaging of labeled red blood cells and plasma. With the use of a live animal glucose clamp, blood cell flow was measured during either hypoglycemia (∼50 mg/dl) or hyperglycemia (∼300 mg/dl). In contrast to the large glucose-dependent islet blood velocity changes observed in wild-type mice, only minimal differences are observed in both Cx36+/− and Cx36−/− mice. This observation supports a novel model where intraislet blood cell flow is regulated by the coordinated electrical activity in the islet β-cells. Because Cx36 expression and function is reduced in type 2 diabetes, the resulting defect in intraislet blood cell flow regulation may also play a significant role in diabetic pathology.

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Section: E328 Connexin 36 Mediates Blood Cell Flow In Isletsmentioning

confidence: 99%

Section: E328 Connexin 36 Mediates Blood Cell Flow In Isletsmentioning

confidence: 99%

Connexin 36 mediates blood cell flow in mouse pancreatic islets

Short

Head

Piston

2014

American Journal of Physiology-Endocrinology and Metabolism

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“…Recent studies have shown that molecules involved in dopamine receptor signaling are expressed not only in the brain but also in both murine and human pancreatic islets [52, 53]. In patients with Parkinson’s disease, treatment with l -DOPA, a dopamine precursor, significantly impairs glucose metabolism in a dose-dependent manner [54, 55].…”

Section: Impact Of a Brown Rice-derived Bioactive Product On Feeding mentioning

confidence: 99%

Expanding frontiers in weight-control research explored by young investigators

et al. 2016

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At the 93rd annual meeting of the Physiological Society of Japan, a symposium entitled “Expanding frontiers in weight-control research explored by young investigators” was organized. The latest research on weight control was presented by young up-and-coming investigators. The symposium consisted of the following presentations: Gastrointestinal brush cells, immunity, and energy homeostasis; Impact of a brown rice-derived bioactive product on feeding regulation and fuel metabolism; A novel G protein-coupled receptor-regulated neuronal signaling pathway triggers sustained orexigenic effects; and NMDA receptor co-agonist d-serine regulates food preference. These four talks presented at the symposium were summarized as a series of short reviews in this review.

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“…A study done recently has shown a negative feedback regulatory circuit for glucose-stimulated insulin secretion in purified human islets in vitro [19] . The release of dopamine and insulin together in response to the glucose load is demonstrated by the in-vitro infusion of dopamine into the insulin-containing secretory granules of human β-cells.…”

Section: +mentioning

confidence: 99%

“…The release of dopamine and insulin together in response to the glucose load is demonstrated by the in-vitro infusion of dopamine into the insulin-containing secretory granules of human β-cells. Dopamine in turn exerts an antagonistic action on the D2 receptors that are also expressed on β-cells and thus inhibiting insulin secretion [19] . Neuroendocrine cells and pancreatic islets take up L-DOPA and convert it into Dopamine by the enzyme DOPA decarboxylase, which is expressed in β-cells of the pancreatic islets [20][21][22][23] .…”

Section: +mentioning

confidence: 99%

Congenital hyperinsulinism: Role of fluorine-18L-3, 4 hydroxyphenylalanine positron emission tomography scanning

Gopal‐Kothandapani

Hussain

2014

WJR

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Congenital hyperinsulinism (CHI) is a rare but complex heterogeneous disorder caused by unregulated secretion of insulin from the β-cells of the pancreas leading to severe hypoglycaemia and neuroglycopaenia. Swift diagnosis and institution of appropriate management is crucial to prevent or minimise adverse neurodevelopmental outcome in children with CHI. Histologically there are two major subtypes of CHI, diffuse and focal disease and the management approach will significantly differ depending on the type of the lesion. Patients with medically unresponsive diffuse disease require a near total pancreatectomy, which then leads on to the development of iatrogenic diabetes mellitus and pancreatic exocrine insufficiency. However patients with focal disease only require a limited pancreatectomy to remove only the focal lesion thus providing complete cure to the patient. Hence the preoperative differentiation of the histological subtypes of CHI becomes paramount in the management of CHI. Fluorine-18L-3, 4-hydroxyphenylalanine positron emission tomography ( 18 F-DOPA-PET) is now the gold standard for pre-operative differentiation of focal from diffuse disease and localisation of the focal lesion. The aim of this review article is to give a clinical overview of CHI, then review the role of dopamine in β-cell physiology and finally discuss the role of

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Dopamine-Mediated Autocrine Inhibitory Circuit Regulating Human Insulin Secretion in Vitro

Cited by 76 publications

References 68 publications

Connexin 36 mediates blood cell flow in mouse pancreatic islets

Connexin 36 mediates blood cell flow in mouse pancreatic islets

Expanding frontiers in weight-control research explored by young investigators

Congenital hyperinsulinism: Role of fluorine-18L-3, 4 hydroxyphenylalanine positron emission tomography scanning

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