Does GLP-1 suppress its own basal secretion?

Elahi, Dariush; Ruff, Dennis; Carlson, Olga D.; Meneilly, Graydon S.; Habener, Joel F.; Egan, Josephine M.

doi:10.3109/07435800.2015.1038353

Cited by 10 publications

(9 citation statements)

References 29 publications

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“…86 Such an elevation in humans would be in line with the 2.2-fold rise in plasma GIP levels evident in our rat mTBI study and could be further augmented by continuous subcutaneous administration of exogenous GIP, as has been achieved in human studies with GLP-1 over an extended period. 87 Notably, administration of exogenous incretins does not appear to suppress their endogenous release, 88 thereby providing our studies translational potential.…”

Section: Discussionmentioning

confidence: 95%

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

Hsieh

Chen

et al. 2016

Journal of Neurotrauma

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Mild traumatic brain injury (mTBI) is a major public health issue, representing 75–90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13–15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.

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Section: Discussionmentioning

confidence: 95%

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

Hsieh

Chen

et al. 2016

Journal of Neurotrauma

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“…The GLP-1 dosage selected for this study was chosen based on the preassumption that basal GLP-1 secretion would not be affected in a negative feedback loop, as previously reported. 32 Chronic GLP-1 intraperitoneal administration did not induce any significant change in body weight, body weight gain, or food intake in SHAM-GLP1 or VGX-GLP1 when compared with the respective controls. GLP-1 has a well-established role in the regulation of food intake and body weight that is partially dependent of the vagus nerve integrity, 13 although GLP-1R agonists were also reported to exert these effects through direct action on the hypothalamus.…”

Section: Discussionmentioning

confidence: 99%

GLP‐1 induces alpha cell proliferation and overrides leptin suppression induced by negative energy balance in vagotomized rats

Morais

Patrı́cio

Pereira

et al. 2019

J of Cellular Biochemistry

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Glucagon‐like peptide‐1 (GLP‐1) influences energy balance by exerting effects on food intake and glucose metabolism, through mechanisms that are partially dependent on the vagal pathway. The aim of this study was to characterize the effects of chronic GLP‐1 stimulation on energy homeostasis and glucose metabolism in the absence of vagal innervation Truncal vagotomized (VGX) and sham operated rats (SHAM) received an intraperitoneal GLP‐1 infusion (3.5 pmol/kg/min) trough mini‐osmotic pumps. To dissect the effects derived from vagal denervation on food intake, an additional group was included consisting of sham operated rats that were PAIR FED to VGX. Food intake and body weight were recorded throughout the experimental period, while the percentage of white and brown adipose tissue, fasting glucose, insulin, gastro‐intestinal hormonal profile, hypothalamic, and BAT gene expression were assessed at endpoint. VGX rats had significantly lower food intake, body weight gain, and leptin levels when compared with SHAM rats. Despite having similar body weight, PAIR‐FED rats had lower fasting leptin, insulin and insulin resistance, while having higher ghrelin levels than VGX. GLP‐1 infusion did not influence food intake or body weight, but was associated with lower leptin levels in VGX and lower pancreatic α‐cells ki‐67 staining in SHAM. Concluding, this study corroborates that the vagus nerve may modulate whole body energy homeostasis by acting in peripheral signals. Our data suggest that in the absence of vagal or parasympathetic tonus, GLP‐1 mediated inhibition of cell proliferation markers in α‐cells is prevented, meanwhile leptin suppression, associated with a negative energy balance, is partially overridden.

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“…Such autocrine feedback may be operative also in GLP-1-secreting cells, where GLP-1R expression on L-cells and its involvement in GLP-1 secretion has previously been suggested by data from in vivo and in vitro studies [77,121]. Although a recent study indicated that GLP-1 and its degradation products do not modulate L-cell basal secretion of GLP-1(7-36) amide, any potential feedback mechanisms acting on post prandial responses were not investigated [122].…”

Section: Neuroendocrine Signalsmentioning

confidence: 92%

The regulation of function, growth and survival of GLP-1-producing L-cells

2015

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Glucagon-like peptide-1 (GLP-1) is a peptide hormone, released from intestinal L-cells in response to hormonal, neural and nutrient stimuli. In addition to potentiation of meal-stimulated insulin secretion, GLP-1 signalling exerts numerous pleiotropic effects on various tissues, regulating energy absorption and disposal, as well as cell proliferation and survival. In Type 2 Diabetes (T2D) reduced plasma levels of GLP-1 have been observed, and plasma levels of GLP-1, as well as reduced numbers of GLP-1 producing cells, have been correlated to obesity and insulin resistance. Increasing endogenous secretion of GLP-1 by selective targeting of the molecular mechanisms regulating secretion from the L-cell has been the focus of much recent research. An additional and promising strategy for enhancing endogenous secretion may be to increase the L-cell mass in the intestinal epithelium, but the mechanisms that regulate the growth, survival and function of these cells are largely unknown. We recently showed that prolonged exposure to high concentrations of the fatty acid palmitate induced lipotoxic effects, similar to those operative in insulin-producing cells, in an in vitro model of GLP-1-producing cells. The mechanisms inducing this lipototoxicity involved increased production of reactive oxygen species (ROS). In this review, regulation of GLP-1-secreting cells is discussed, with a focus on the mechanisms underlying GLP-1 secretion, long-term regulation of growth, differentiation and survival under normal as well as diabetic conditions of hypernutrition.

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Does GLP-1 suppress its own basal secretion?

Cited by 10 publications

References 29 publications

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats

GLP‐1 induces alpha cell proliferation and overrides leptin suppression induced by negative energy balance in vagotomized rats

The regulation of function, growth and survival of GLP-1-producing L-cells

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