Parasympathetic and sympathetic control of the pancreas: A role for the suprachiasmatic nucleus and other hypothalamic centers that are involved in the regulation of food intake

Buijs, Ruud M.; Chun, Soo Jin; Niijima, Akira; Romijn, H.J.; Nonomura, Katsuya

doi:10.1002/1096-9861(20010319)431:4<405::aid-cne1079>3.0.co;2-d

Cited by 286 publications

(218 citation statements)

References 79 publications

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“…Our finding of a circadian phase effect on early-phase insulin secretion could be mediated through the circadian system via numerous mechanisms. First, there are multisynaptic projections from the SCN to the pancreas (33,34). Second, pancreatic cells contain circadian clocks and their disruption, by knocking out circadian clock gene Brain and muscle Arnt-like protein-1 (BMAL1) specifically within the pancreas, results in decreased insulin secretion and impaired glucose tolerance (21,23).…”

Section: Discussionmentioning

confidence: 90%

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Morris

Yang

Garcia

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

351

336

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Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/ feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show-by using two 8-d laboratory protocols-in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower earlyphase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.circadian disruption | shift work | night work | glucose metabolism | diabetes I n healthy humans, there is a strong time-of-day variation in glucose tolerance, with a peak in the morning and a trough in the evening and night (1-6). Understanding the underlying mechanisms of the day/night variation in glucose tolerance is important for diurnally active individuals as well as shift workers, who are at increased risk for developing type 2 diabetes (7-9). The endogenous circadian system and circadian misalignment (i.e., misalignment between the endogenous circadian system and 24-h environmental/behavioral cycles) have been shown to affect glucose metabolism (4,(10)(11)(12)(13)(14). However, the relative and separate importance of the endogenous circadian system and circadian misalignment-after accounting for behavioral cycle effects (including the sleep/wake, fasting/feeding, and physical inactivity/activity cycles, etc.)-on 24-h variation in glucose tolerance is not well understood.Most species have evolved an endogenous circadian timing system that optimally times physiological variations and behaviors relative to the 24-h environmental cycle (15-17). The mammalian circadian system is comp...

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Section: Discussionmentioning

confidence: 90%

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Morris

Yang

Garcia

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

351

336

View full text Add to dashboard Cite

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“…15 Neuropeptide Y-and proopiomelanocortinexpressing neurons in the arcuate nucleus affect glucose metabolism via their projections to (pre-autonomic) hypothalamic neurons that control the autonomic nervous input to various peripheral organs, such as the pancreas. 25 Thus, it could well be that alterations in the brain in rats on a freechoice HFHS diet are mediating the effects on glucose metabolism via the ANS.…”

Section: Discussionmentioning

confidence: 92%

“…The pancreas is innervated by the ANS and it has been shown that the hypothalamus may regulate this sensitivity via this ANS innervation. [25][26][27][28] The latter hypothesis is supported by our recent finding that centrally, neuropeptide Y and proopiomelanocortin mRNA expression in the arcuate nucleus were altered in HFHS-choice diet rats in such a direction that it promotes glucose intolerance and insulin resistance. 15 Neuropeptide Y-and proopiomelanocortinexpressing neurons in the arcuate nucleus affect glucose metabolism via their projections to (pre-autonomic) hypothalamic neurons that control the autonomic nervous input to various peripheral organs, such as the pancreas.…”

Section: Discussionmentioning

confidence: 99%

A free-choice high-fat high-sugar diet induces glucose intolerance and insulin unresponsiveness to a glucose load not explained by obesity

et al. 2010

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Objectives: In diet-induced obesity, it is not clear whether impaired glucose metabolism is caused directly by the diet, or indirectly via obesity. This study examined the effects of different free-choice, high-caloric, obesity-inducing diets on glucose metabolism. In these free-choice diets, saturated fat and/or a 30% sugar solution are provided in an addition to normal chow pellets. Method: In the first experiment, male rats received a free-choice high-fat high-sugar (HFHS), free-choice high-fat (HF) or a chow diet. In a second experiment, male rats received a free-choice high-sugar (HS) diet or chow diet. For both experiments, after weeks 1 and 4, an intravenous glucose tolerance test was performed. Results: Both the HFHS and HF diets resulted in obesity with comparable plasma concentrations of free fatty acids. Interestingly, the HF diet did not affect glucose metabolism, whereas the HFHS diet resulted in hyperglycemia, hyperinsulinemia and in glucose intolerance because of a diminished insulin response. Moreover, adiposity in rats on the HF diet correlated positively with the insulin response to the glucose load, whereas adiposity in rats on the HFHS diet showed a negative correlation. In addition, total caloric intake did not explain differences in glucose tolerance. To test whether sugar itself was crucial, we next performed a similar experiment in rats on the HS diet. Rats consumed three times as much sugar when compared with rats on the HFHS diet, which resulted in obesity with basal hyperinsulinemia. Glucose tolerance, however, was not affected. Conclusion: Together, these results suggest that not only obesity or total caloric intake, but the diet content also is crucial for the glucose intolerance that we observed in rats on the HFHS diet.

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“…For example, bilateral VMN lesioning induces hyperinsulinemia (49,50) whereas electrical stimulation of the VMN suppresses glucose-induced insulin secretion (51). Further, the VMN is known to regulate autonomic outflow to the pancreas (52,53), and activation of islet sympathetic nerves during glycopenic stress (54) inhibits insulin secretion via a mechanism involving activation of α2-adrenoreceptors on the beta cell (47,48). However, the neurocircuitry that underlies inhibitory control of insulin secretion by the brain remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Functional identification of a neurocircuit regulating blood glucose

Meek

Nelson

Matsen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

153

187

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Previous studies implicate the hypothalamic ventromedial nucleus (VMN) in glycemic control. Here, we report that selective inhibition of the subset of VMN neurons that express the transcription factor steroidogenic-factor 1 (VMN SF1 neurons) blocks recovery from insulin-induced hypoglycemia whereas, conversely, activation of VMN SF1 neurons causes diabetes-range hyperglycemia. Moreover, this hyperglycemic response is reproduced by selective activation of VMN SF1 fibers projecting to the anterior bed nucleus of the stria terminalis (aBNST), but not to other brain areas innervated by VMN SF1 neurons. We also report that neurons in the lateral parabrachial nucleus (LPBN), a brain area that is also implicated in the response to hypoglycemia, make synaptic connections with the specific subset of glucoregulatory VMN SF1 neurons that project to the aBNST. These results collectively establish a physiological role in glucose homeostasis for VMN SF1 neurons and suggest that these neurons are part of an ascending glucoregulatory LPBN→VMN SF1 →aBNST neurocircuit.glucoregulatory circuit | counter regulation | ventromedial nucleus | bed nucleus of the stria terminalis | hyperglycemia B ecause the brain relies exclusively on glucose as a fuel source, brain function is rapidly compromised when circulating glucose levels drop below the normal range. Consequently, hypoglycemia elicits a robust, integrated, and redundant set of counterregulatory responses (CRRs) that ensure the rapid and efficient recovery of plasma glucose concentrations into the normal range (1). Components of the CRR include increased secretion of the hormones glucagon, epinephrine, and glucocorticoids, inhibition of glucoseinduced insulin secretion, increased sympathetic nervous system (SNS) outflow to the liver, and increased food intake (1-3). Owing to this redundancy, recovery from hypoglycemia is difficult to block in normal humans and animal models, even when adrenal or glucagon responses are prevented. Only when multiple responses are blocked is the ability to recover from hypoglycemia significantly compromised (4). This arrangement is perhaps unsurprising, given the threat to survival posed by hypoglycemia.Although glucose sensing can occur at peripheral (e.g., neurons innervating the hepatic portal vein) as well as central sites (3, 5), the brain is the organ responsible both for transducing this information into effective glucose counterregulation and for terminating this response once euglycemia is restored. Of the many brain areas that have been investigated, the hypothalamic ventromedial nucleus (VMN) has emerged as potentially being both necessary and sufficient to elicit this powerful response. This assertion is based on evidence that, whereas electrical stimulation of the VMN activates the CRR and thereby raises circulating glucose levels (6), glucose infusion directly into the VMN can suppress the CRR during hypoglycemia (7) and thereby impair recovery of normal blood glucose levels (8). Moreover, two recent papers identified a circuit comprise...

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Parasympathetic and sympathetic control of the pancreas: A role for the suprachiasmatic nucleus and other hypothalamic centers that are involved in the regulation of food intake

Cited by 286 publications

References 79 publications

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

A free-choice high-fat high-sugar diet induces glucose intolerance and insulin unresponsiveness to a glucose load not explained by obesity

Functional identification of a neurocircuit regulating blood glucose

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