| 1. |
- Ahlkvist, Linda, et al.
(författare)
-
Synergism by individual macronutrients explains the marked early GLP-1 and islet hormone responses to mixed meal challenge in mice
- 2012
-
Ingår i: Regulatory Peptides. - : Elsevier. - 0167-0115 .- 1873-1686. ; 178:1-3, s. 29-35
-
Tidskriftsartikel (refereegranskat)abstract
- Apart from glucose, proteins and lipids also stimulate incretin and islet hormone secretion. However, the glucoregulatory effect of macronutrients in combination is poorly understood. We therefore developed an oral mixed meal model in mice to 1) explore the glucagon-like peptide-1 (GLP-1) and islet hormone responses to mixed meal versus isocaloric glucose, and 2) characterize the relative contribution of individual macronutrients to these responses. Anesthetized C57BL/6J female mice were orally gavaged with 1) a mixed meal (0.285 kcal; glucose, whey protein and peanut oil; 60/20/20% kcal) versus an isocaloric glucose load (0.285 kcal), and 2) a mixed meal (0.285 kcal) versus glucose, whey protein or peanut oil administered individually in their mixed meal caloric quantity, i.e., 0.171, 0.055 and 0.055 kcal, respectively. Plasma was analyzed for glucose, insulin and intact GLP-1 before and during oral challenges. Plasma glucose was lower after mixed meal versus after isocaloric glucose ingestion. In spite of this, the peak insulin response (P=0.02), the peak intact GLP-1 levels (P=0.006) and the estimated β-cell function (P=0.005) were higher. Furthermore, the peak insulin (P=0.004) and intact GLP-1 (P=0.006) levels were higher after mixed meal ingestion than the sum of responses to individual macronutrients. Compared to glucose alone, we conclude that there is a marked early insulin response to mixed meal ingestion, which emanates from a synergistic, rather than an additive, effect of the individual macronutrients in the mixed meal and is in part likely caused by increased levels of GLP-1.
|
|
| 2. |
|
|
| 3. |
- Ahrén, Bo
(författare)
-
The neuro-incretin concept.
- 2014
-
Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 194:Sep 16, s. 3-5
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
- Banke, Elin, et al.
(författare)
-
Cocaine- and amphetamine-regulated transcript is expressed in adipocytes and regulate lipid- and glucose homeostasis.
- 2013
-
Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 182:Jan.,11, s. 35-40
-
Tidskriftsartikel (refereegranskat)abstract
- Cocaine- and amphetamine-regulated transcript (CART) is a regulatory peptide expressed in the nervous system and in endocrine cells, e.g. in pancreatic islets. CART deficient mice exhibit islet dysfunction, impaired insulin secretion and increased body weight. A mutation in the CART gene in humans is associated with reduced metabolic rate, obesity and diabetes. Furthermore, CART is upregulated in islets of type-2 diabetic rats and regulates islet hormone secretion in vitro. While the function of CART in the nervous system has been extensively studied, there is no information on its expression or function in white adipose tissue. CART mRNA and protein were found to be expressed in both subcutaneous and visceral white adipose tissues from rat and man. Stimulating rat primary adipocytes with CART significantly potentiated isoprenaline-induced lipolysis, and hormone sensitive lipase activation (phosphorylation of Ser 563). On the other hand, CART significantly potentiated the inhibitory effect of insulin on isoprenaline-induced lipolysis. CART inhibited insulin-induced glucose uptake, which was associated with inhibition of PKB phosphorylation. In conclusion, CART is a novel constituent of human and rat adipocytes and affects several biological processes central in both lipid- and glucose homeostasis. Depending on the surrounding conditions, the effects of CART are insulin-like or insulin-antagonistic.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Ericsson, Peter, et al.
(författare)
-
Gastrin release: Antrum microdialysis reveals a complex neural control.
- 2010
-
Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 161, s. 22-32
-
Tidskriftsartikel (refereegranskat)abstract
- We used microdialysis to monitor local gastrin release in response to food, acid blockade and acute vagal excitation. For the first time, gastrin release has been monitored continuously in intact conscious rats in a physiologically relevant experimental setting in a fashion that minimizes confounding systemic effects. Microdialysis probes were placed in the submucosa on either side of the antrum, 3days before the experiments. The concentration of gastrin in the antral submucosal compartment was 5-10 times higher than in serum regardless of the prandial state. The rats were conscious during microdialysis except when subjected to electrical vagal stimulation. Acid blockade (omeprazole treatment of freely fed rats for 4days), or bilateral sectioning of the abdominal vagal trunks (fasted rats), raised the gastrin concentration in blood as well as microdialysate. The high gastrin concentration following omeprazole treatment was not affected by vagotomy. Vagal excitation stimulated the G cells: electrical vagal stimulation and pylorus ligation (fasted rats) raised the gastrin concentration transiently in both serum and microdialysate. Food intake induced a 2- to 3-fold increase in serum gastrin, while gastrin in antral microdialysate increased 10- to 15-fold. In unilaterally vagotomized rats, food evoked a prompt peak gastrin release followed by a gradual decline on the intact side. On the vagotomized side of the antrum, the peak response seemed to be reduced while the microdialysate gastrin concentration remained elevated. Thus, unilateral vagotomy surprisingly raised the integrated gastrin response to food on the denervated side compared to the intact side, indicating that vagotomy suppresses an inhibitory as well as a stimulating effect on the G cells. While local infusion of atropine was without effect, infusion of the neuronal blocker tetrodotoxin (TTX) (which had no effect on basal gastrin) virtually abolished the food-evoked gastrin response and lowered the high microdialysate gastrin concentration in omeprazole-treated rats by 65%. We conclude that activated gastrin release, unlike basal gastrin release, is highly dependent on a neural input: 1) Vagal excitation has a transient stimulating effect on the G cells. The transient nature of the response suggests that the vagus has not only a prompt stimulatory but also a slow inhibitory effect on gastrin release. 2) Although vagal denervation did not affect the gastrin response to anacidity, the TTX experiments revealed that both food-evoked and anacidity-evoked gastrin release depends on neural input.
|
|
| 9. |
- Ericsson, Peter, et al.
(författare)
-
Gastrin response to candidate messengers in intact conscious rats monitored by antrum microdialysis.
- 2010
-
Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 163, s. 24-30
-
Tidskriftsartikel (refereegranskat)abstract
- We monitored gastrin release in response to locally applied candidate messengers in intact conscious rats. Earlier studies have been performed on anaesthetized animals, isolated pieces of antrum, or purified preparations of gastrin cells. In this study we created an experimental situation to resemble physiological conditions, using reverse microdialysis to administer regulatory peptides and amines that might affect gastrin secretion. Microdialysis probes were implanted in the submucosa of the antrum of the rat stomach. Three days later, putative messenger compounds were administered via the probe. Their effects on basal (24h fast) and omeprazole-stimulated (400mumol/kg/day, 4days peroral administration) gastrin release were monitored by continuous measurement (3h) of gastrin in the perfusate (radioimmunoassay). Fasted rats (low microdialysate gastrin, 2.1+/-0.1pmoll(-1)) were used to study stimulation of gastrin release. Omeprazole-treated rats (high microdialysate gastrin, 95.8+/-6.7pmoll(-1)) were used to study suppression of gastrin release. The following agents raised the concentration of microdialysate gastrin (peak response): gastrin-releasing peptide (GRP) (11-fold increase at a near-maximal dose), carbachol (5-fold increase), serotonin (2-fold increase) and isoprenaline (20-fold increase). Adrenaline and noradrenaline induced transient but powerful elevation (40- and 20-fold increase). Somatostatin, galanin and bradykinin (at near-maximal doses) suppressed omeprazole-stimulated gastrin release (50% decrease). Calcitonin gene-related peptide, ghrelin, gastric inhibitory peptide, motilin, neurotensin, neuromedin U-25, peptide YY and vasoactive intestinal peptide were without effect on gastrin release, as were aspartate, gamma-aminobutyric acid, glutamate, glycine, dopamine and histamine. The results support the view that G cells operate under neurocrine/paracrine control. They were stimulated by agents present in enteric neurons (GRP, galanin, choline ester and catechol amines) and in gastric endocrine cells (serotonin). They were inhibited by somatostatin (D cell peptide), galanin (neuropeptide) and by the inflammatory agent bradykinin.
|
|
| 10. |
- Erlanson-Albertsson, Charlotte, et al.
(författare)
-
Fructose affects enzymes involved in the synthesis and degradation of hypothalamic endocannabinoids.
- 2010
-
Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 161, s. 87-91
-
Tidskriftsartikel (refereegranskat)abstract
- Endocannabinoids have been implicated in the regulation of consumption of palatable food, sugar in particular. In this study, we investigated how palatable solutions would affect the hypothalamic mRNA expression of enzymes involved in the synthesis and degradation of the two main endocannabinoids, anandamide and 2-arachidonoyl-glycerol. Rats were offered sugar solutions to drink for one week, during which daily food and drink intake, and body weight gain was monitored. Rats offered sugar solutions to drink consumed less solid food but drank more of their respective sugar solution than did water-drinking control rats, resulting in increased total calorie intake. However, this increase in caloric intake did not result in increased body weight or adiposity in the rats. The mRNA expression of fatty acid amid hydrolase was up-regulated by sucrose and fructose. N-acyl phospatidyl ethanolamine phospholipase D mRNA was up-regulated by sucrose, whereas phospholipase C was down-regulated by all forms of sugar tested. The mRNA expression of monoglyceride lipase was down-regulated by all three forms of sugar. Also, the mRNA expression of diacylglycerol lipase 1alpha was down-regulated by sucrose and fructose, whereas the mRNA expression of diacylglycerol lipase 1beta was up-regulated by fructose. In this study, we show that sugars in liquid form affect enzymes involved in the degradation and synthesis of endocannabinoids in the hypothalamus and that this effect predates obesity.
|
|
