Hypothalamic control of energy and glucose metabolism

Sisley, Stephanie; Sandoval, Darleen A.

doi:10.1007/s11154-011-9189-x

Cited by 38 publications

(32 citation statements)

References 190 publications

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“…It is possible that in the RIP-GRP78 −/+ mouse the effect on weight gain may relate to insulin's known effects in the hypothalamus (i.e. controlling body weight by reducing food intake and increasing energy expenditure) [39,40]. We did not observe a significant effect on food intake in control vs transgenic male mice, thus perhaps increased energy expenditure or reduced hyperinsulinaemia may account for the difference in body-weight gain and fat accumulation.…”

Section: Discussioncontrasting

confidence: 53%

GRP78 overproduction in pancreatic beta cells protects against high-fat-diet-induced diabetes in mice

et al. 2013

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Aims/hypothesis Endoplasmic reticulum (ER) stress has been detected in pancreatic beta cells and in insulinsensitive tissues, such as adipose and liver, in obesitylinked rodent models of type 2 diabetes. The contribution of ER stress to pancreatic beta cell dysfunction in type 2 diabetes is unclear. We hypothesised that increased chaperone capacity protects beta cells from ER stress and dysfunction caused by obesity and improves overall glucose homeostasis. Methods We generated a mouse model that overproduces the resident ER chaperone GRP78 (glucose-regulated protein 78 kDa) in pancreatic beta cells under the control of a rat insulin promoter. These mice were subjected to high-fat diet (HFD) feeding for 20 weeks and metabolic variables and markers of ER stress in islets were measured. Results As expected, control mice on the HFD developed obesity, glucose intolerance and insulin resistance. In contrast, GRP78 transgenic mice tended to be leaner than their non-transgenic littermates and were protected against development of glucose intolerance, insulin resistance and ER stress in islets. Furthermore, islets from transgenic mice had a normal insulin content and normal levels of cell-surface GLUT2 (glucose transporter 2) and the transgenic mice were less hyperinsulinaemic than control mice on the HFD. Conclusions/interpretation These data show that increased chaperone capacity in beta cells provides protection against the pathogenesis of obesity-induced type 2 diabetes by maintaining pancreatic beta cell function, which ultimately improves whole-body glucose homeostasis.

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Section: Discussioncontrasting

confidence: 53%

GRP78 overproduction in pancreatic beta cells protects against high-fat-diet-induced diabetes in mice

et al. 2013

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“…Central insulin alters food intake and energy expenditure (19,106,108) and systemic glucose responses to meals and fluctuations of plasma glucose (51,78,113). Insulin in the brain is also involved in reproductive function/development (28), hedonic responses (49), and sympathetic activity (101,134).…”

Section: The Functions Of Central Insulinmentioning

confidence: 99%

Interactions between the central nervous system and pancreatic islet secretions: a historical perspective

Begg

Woods

2013

Advances in Physiology Education

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The endocrine pancreas is richly innervated with sympathetic and parasympathetic projections from the brain. In the mid-20th century, it was established that α-adrenergic activation inhibits, whereas cholinergic stimulation promotes, insulin secretion; this demonstrated the importance of the sympathetic and parasympathetic systems in pancreatic endocrine function. It was later established that insulin injected peripherally could act within the brain, leading to the discovery of insulin and insulin receptors within the brain and the receptor-mediated transport of insulin into the central nervous system from endothelial cells. The insulin receptor within the central nervous system is widely distributed, reflecting insulin's diverse range of actions, including acting as an adiposity signal to reduce food intake and increase energy expenditure, regulation of systemic glucose responses, altering sympathetic activity, and involvement in cognitive function. As observed with central insulin administration, the pancreatic hormones glucagon, somatostatin, pancreatic polypeptide, and amylin can each also reduce food intake. Pancreatic and also gut hormones are released cephalically, in what is an important mechanism to prepare the body for a meal and prevent excessive postprandial hyperglycemia.

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“…Many neurotransmitters, neuropeptides, enzymes and molecules which participate intracellular signaling in the hypothalamus are reported to regulate glucose homeostasis [7,8,9,10,11,12]. Among them, adenosine 5′-monophosphate-activated protein kinase (AMPK) is one of the main regulators of energy homeostasis including glucose metabolism [13,14,15,16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Olanzapine-Induced Hyperglycemia: Possible Involvement of Histaminergic, Dopaminergic and Adrenergic Functions in the Central Nervous System

et al. 2013

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Background/Aims: Atypical antipsychotic drugs such as olanzapine are known to induce metabolic disturbance. We have already shown that olanzapine induces hepatic glucose production through the activation of hypothalamic adenosine 5′-monophosphate-activated protein kinase (AMPK). However, it is unclear how olanzapine activates hypothalamic AMPK. Since olanzapine is known to antagonize several receptors, including histaminergic, muscarinic, serotonergic, dopaminergic and adrenergic receptors, we examined the effect of each receptor antagonist on blood glucose levels in mice. Moreover, we also investigated whether these antagonists activate hypothalamic AMPK. Methods: Male 6-week-old ICR mice were used. Blood glucose levels were determined by the glucose oxidase method. AMPK expression was measured by Western blotting. Results: Central administration of olanzapine (5-15 nmol i.c.v.) dose-dependently increased blood glucose levels in mice, whereas olanzapine did not change blood insulin levels. Histamine H₁ receptor antagonist chlorpheniramine (1-10 μg i.c.v.), dopamine D₂ receptor antagonist L-sulpiride (1-10 μg i.c.v.) and α₁-adrenoceptor antagonist prazosin (0.3-3 μg i.c.v.) also significantly increased blood glucose levels in mice. In contrast, the blood glucose levels were not affected by muscarinic M₁ receptor antagonist dicyclomine (1-10 μg i.c.v.) or serotonin 5-HT_2A receptor antagonist M100907 (1-10 ng i.c.v.). Olanzapine-induced hyperglycemia was inhibited by the AMPK inhibitor compound C, and AMPK activator AICAR (10 ng to 1 μg i.c.v.) significantly increased blood glucose levels. Olanzapine (15 nmol), chlorpheniramine (10 μg), L-sulpiride (10 μg) and prazosin (3 μg) significantly increased phosphorylated AMPK in the hypothalamus of mice. Conclusion: These results suggest that olanzapine activates hypothalamic AMPK by antagonizing histamine H₁ receptors, dopamine D₂ receptors and α₁-adrenoceptors, which induces hyperglycemia.

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Hypothalamic control of energy and glucose metabolism

Cited by 38 publications

References 190 publications

GRP78 overproduction in pancreatic beta cells protects against high-fat-diet-induced diabetes in mice

GRP78 overproduction in pancreatic beta cells protects against high-fat-diet-induced diabetes in mice

Interactions between the central nervous system and pancreatic islet secretions: a historical perspective

Olanzapine-Induced Hyperglycemia: Possible Involvement of Histaminergic, Dopaminergic and Adrenergic Functions in the Central Nervous System

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