A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity

Mencarelli, Monica; Zulian, Alessandra; Cancello, Raffaella; Alberti, Luisella; Gilardini, Luisa; Blasio, Anna Maria Di; Invitti, Cecilia

doi:10.1038/ejhg.2012.103

Cited by 32 publications

(21 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the present study, ob/ob mice displayed similar abnormal glucose and lipid metabolism and oxidative stress, which were highly consistent with our previous studies in overweight adolescents [14] and clinical studies that have indicated that obese patients are more susceptible to impaired glucose tolerance and an early-onset diabetes [15]. Recent studies by Gurzov et al have reported that oxidative stress accompanying obesity inactivates proteintyrosine phosphatases (PTPs) in the liver, thus activating select signaling pathways that exacerbate disease progression [16].…”

Section: The Impairment Of β Cell Function Induced By Oxidative Stressupporting

confidence: 93%

Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity

Zhou

Yu²,

Shen³

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: The aim of this study was to clarify the relationship among Rac1 expression and activation, oxidative stress and β cell dysfunction in obesity. Methods: In vivo, serum levels of glucose, insulin, oxidative stress markers and Rac1 expression were compared between ob/ob mice and C57BL/6J controls. Then, these variables were rechecked after the administration of the specific Rac1 inhibitor-NSC23766 in ob/ob mice. In vitro, NIT-1 β cells were cultured in a hyperglycemic and/or hyperlipidemic state with or without NSC23766, and the differences of Rac1 expression and translocation, NADPH oxidase(Nox) enzyme activity, reactive oxygen species (ROS) and insulin mRNA were observed. Results: ob/ob mice displayed abnormal glycometabolism, oxidative stress and excessive expression of Rac1 in the pancreas. NSC23766 injection inhibited the expression of Rac1 in the pancreas, along with amelioration of oxidative stress and glycometabolism in obese mice. Under hyperglycemic and/or hyperlipidemic conditions, Rac1 translocated to the cellular membrane, induced activation of the NADPH oxidase enzyme and oxidative stress, and simultaneously reduced the insulin mRNA expression in NIT-1 β cells. Inhibiting Rac1 activity could alleviate oxidative stress and meliorate the decline of insulin mRNA in β cells. Conclusions: Rac1 might contribute to oxidative stress systemically and locally in the pancreas in obesity. The excessive activation and expression of Rac1 in obesity were associated with β cell dysfunction through ROS production.

show abstract

Section: The Impairment Of β Cell Function Induced By Oxidative Stressupporting

confidence: 93%

Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity

Zhou

Yu²,

Shen³

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Knockout of the MC4 receptor also results in obesity in rodents (Huszar et al, 1997). In parallel, severe human obesity can be caused by mutations in genes coding for POMC or its melanocortin receptors (Hager et al, 1998; Yeo et al,2000; Krude et al,2003; Mencarelli et al, 2012). …”

Section: Neuropeptide Modulation Of Gaba and Glutamate Synaptic Actionsmentioning

confidence: 99%

Neuropeptide Transmission in Brain Circuits

Pol

2012

Neuron

680

448

View full text Add to dashboard Cite

Neuropeptides are found in many mammalian CNS neurons where they play key roles in modulating neuronal activity. In contrast to amino acid transmitter release at the synapse, neuropeptide release is not restricted to the synaptic specialization, and after release, a neuropeptide may diffuse some distance to exert its action through a G-protein coupled receptor. Some neuropeptides such as hypocretin/orexin are synthesized only in single regions of the brain, and the neurons releasing these peptides probably have similar functional roles. Other peptides such as neuropeptide Y (NPY) are synthesized throughout the brain, and neurons that synthesize the peptide in one region have no anatomical or functional connection with NPY neurons in other brain regions. Here, I review converging data revealing a complex interaction between slow-acting neuromodulator peptides and fast-acting amino acid transmitters in the control of energy homeostasis, drug addiction, mood and motivation, sleep-wake states, and neuroendocrine regulation.

show abstract

“…NPY deficiency attenuates responses to a palatable high fat diet in mice (Hollopeter et al, 1998;Patel et al, 2006). Animals in which POMC neurons have been knocked out are obese and hyperphagic (Butler and Cone, 2002;Mencarelli et al, 2012;Diané et al, 2014;Raffan et al, 2016). Additionally, the release of these neuropeptides is closely associated with dietary fat level.…”

Section: Introductionmentioning

confidence: 99%

Dietary fat alters the response of hypothalamic neuropeptide Y to subsequent energy intake in broiler chickens

Wang

Liu

et al. 2016

Journal of Experimental Biology

View full text Add to dashboard Cite

Dietary fat affects appetite and appetite-related peptides in birds and mammals; however, the effect of dietary fat on appetite is still unclear in chickens faced with different energy statuses. Two experiments were conducted to investigate the effects of dietary fat on food intake and hypothalamic neuropeptides in chickens subjected to two feeding states or two diets. In Experiment 1, chickens were fed a high-fat (HF) or low-fat (LF) diet for 35 days, and then subjected to fed (HF-fed, LF-fed) or fasted (HF-fasted, LF-fasted) conditions for 24 h. In Experiment 2, chickens that were fed a HF or LF diet for 35 days were fasted for 24 h and then re-fed with HF (HF-RHF, LF-RHF) or LF (HF-RLF, LF-RLF) diet for 3 h. The results showed that chickens fed a HF diet for 35 days had increased body fat deposition despite decreasing food intake even when the diet was altered during the re-feeding period (P<0.05). LF diet (35 days) promoted agouti-related peptide (AgRP) expression compared with HF diet (P<0.05) under both fed and fasted conditions. LF-RHF chickens had lower neuropeptide Y (NPY) expression compared with LF-RLF chickens; conversely, HF-RHF chickens had higher NPY expression than HF-RLF chickens (P<0.05). These results demonstrate: (1) that HF diet decreases food intake even when the subsequent diet is altered; (2) the orexigenic effect of hypothalamic AgRP; and (3) that dietary fat alters the response of hypothalamic NPY to subsequent energy intake. These findings provide a novel view of the metabolic perturbations associated with long-term dietary fat over-ingestion in chickens.

show abstract

A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity

Cited by 32 publications

References 37 publications

Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity

Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity

Neuropeptide Transmission in Brain Circuits

Dietary fat alters the response of hypothalamic neuropeptide Y to subsequent energy intake in broiler chickens

Contact Info

Product

Resources

About