In vitro insulin treatment reverses changes elicited by nutrients in cellular metabolic processes that regulate food intake in fish

The cardiac effects of exogenously administered insulin for the treatment of diabetes (DM) have recently attracted much attention. In particular, it has been questioned whether insulin is the appropriate treatment for patients with type 2 diabetes mellitus and heart failure. While several old and some new studies suggested that insulin treatment has beneficial effects on the heart, recent observational studies indicate associations of insulin treatment with an increased risk of developing or worsening of pre-existing heart failure and higher mortality rates. However, there is actually little evidence that the associations of insulin administration with any adverse outcomes are causal. On the other hand, insulin clearly causes weight gain and may also cause serious episodes of hypoglycemia. Moreover, excess of insulin (hyperinsulinemia), as often seen with the use of injected insulin, seems to predispose to inflammation, hypertension, dyslipidemia, atherosclerosis, heart failure, and arrhythmias. Nevertheless, it should be stressed that most of the data concerning the effects of insulin on cardiac function derive from in vitro studies with isolated animal hearts. Therefore, the relevance of the findings of such studies for humans should be considered with caution. In the present review, we summarize the existing data about the potential positive and negative effects of insulin on the heart and attempt to answer the question whether any adverse effects of insulin or the consequences of hyperglycemia are more important and may provide a better explanation of the close association of DM with heart failure.

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Effects of Bacterial CLPB Protein Fragments on Food Intake and PYY Secretion

Nutrients ◽

10.3390/nu13072223 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2223

Author(s):

Manon Dominique ◽

Nicolas Lucas ◽

Romain Legrand ◽

Illona-Marie Bouleté ◽

Christine Bôle-Feysot ◽

...

Keyword(s):

Food Intake ◽

Peptide Yy ◽

Molecular Mimicry ◽

Potential Effect ◽

In Vivo Studies ◽

Sprague Dawley ◽

E Coli ◽

In Vivo Effects

CLPB (Caseinolytic peptidase B) protein is a conformational mimetic of α-MSH, an anorectic hormone. Previous in vivo studies have already shown the potential effect of CLPB protein on food intake and on the production of peptide YY (PYY) by injection of E. coli wild type (WT) or E. coli ΔClpB. However, until now, no study has shown its direct effect on food intake. Furthermore, this protein can fragment naturally. Therefore, the aim of this study was (i) to evaluate the in vitro effects of CLPB fragments on PYY production; and (ii) to test the in vivo effects of a CLPB fragment sharing molecular mimicry with α-MSH (CLPB25) compared to natural fragments of the CLPB protein (CLPB96). To do that, a primary culture of intestinal mucosal cells from male Sprague–Dawley rats was incubated with proteins extracted from E. coli WT and ΔCLPB after fragmentation with trypsin or after a heat treatment of the CLPB protein. PYY secretion was measured by ELISA. CLPB fragments were analyzed by Western Blot using anti-α-MSH antibodies. In vivo effects of the CLPB protein on food intake were evaluated by intraperitoneal injections in male C57Bl/6 and ob/ob mice using the BioDAQ® system. The natural CLPB96 fragmentation increased PYY production in vitro and significantly decreased cumulative food intake from 2 h in C57Bl/6 and ob/ob mice on the contrary to CLPB25. Therefore, the anorexigenic effect of CLPB is likely the consequence of enhanced PYY secretion.

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14-3-3 Facilitates Insulin-Stimulated Intracellular Trafficking of Insulin Receptor Substrate 1

Molecular Endocrinology ◽

10.1210/mend.16.3.0790 ◽

2002 ◽

Vol 16 (3) ◽

pp. 552-562 ◽

Cited By ~ 17

Author(s):

Xiaoqin Xiang ◽

Mingsheng Yuan ◽

Ying Song ◽

Neil Ruderman ◽

Rong Wen ◽

...

Keyword(s):

Insulin Receptor ◽

Intracellular Trafficking ◽

High Speed ◽

Insulin Treatment ◽

Insulin Receptor Substrate ◽

Insulin Receptor Substrate 1 ◽

Integral Role ◽

Endogenous Proteins

Abstract The appearance of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and PI3K in a high-speed pellet fraction (HSP) is thought to be a key event in insulin action. Conversely, the disappearance of the IRS-1/PI3K complex from this fraction has been linked to insulin desensitization. The present study examines the role of 14-3-3, a specific phospho-serine binding protein, in mediating the disappearance of IRS-1 from the HSP after insulin treatment. An in vitro pull-down assay using recombinant 14-3-3 revealed that insulin enhances the association of 14-3-3 with IRS-1 in cultured adipocytes and that this is completely inhibited by wortmannin. An association of IRS-1 and 14-3-3 was also observed and was maximal after stimulation by insulin, when endogenous proteins were immunoprecipitated. Epidermal growth factor (EGF), 12-O-tetradecanoylphorbol-13-acetate, and okadaic acid, other agents that cause serine/threonine phosphorylation of IRS-1, also stimulated IRS binding to 14-3-3. The enhancement of IRS-1 binding to 14-3-3 by insulin was accompanied by movement of IRS-1 and the p85 subunit of PI3K from the HSP to the cytosol. In keeping with a key role of 14-3-3 in mediating this redistribution of IRS-1, the complexes of IRS-1 and 14-3-3 were found in the cytosol but not in the HSP of insulin-treated cells. In addition, colocalization of IRS-1 and 14-3-3 was observed in the cytoplasm after insulin treatment by confocal microscopy. Finally, the addition of a phosphorylated 14-3-3 binding peptide to an adipocyte homogenate (to remove 14-3-3 from IRS-1) increased the abundance of IRS-1/PI3K complexes in the HSP and decreased their abundance in the cytosol. These findings strongly suggest that 14-3-3 participates in the intracellular trafficking of IRS-1 by promoting the displacement of serine-phosphorylated IRS-1 from particular structures. They also suggest that 14-3-3 proteins could play an integral role in the process of insulin desensitization.

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Digestion of timothy silage and hay in reindeer

Rangifer ◽

10.7557/2.18.1.1444 ◽

1998 ◽

Vol 18 (1) ◽

pp. 35

Author(s):

R. Moen ◽

M. A. Olsen ◽

Ø. E. Haga ◽

W. Sørmo ◽

T. H. Aagnes Utsi ◽

...

Keyword(s):

Food Intake ◽

Rangifer Tarandus ◽

Rumen Fluid ◽

Total Concentration ◽

Phleum Pratense ◽

Water Soluble ◽

Soluble Carbohydrates ◽

Energy Deficiency

Leafy timothy (Phleum pratense) silage (S), silage mixed with molasses (SM) and hay (H) were fed to nine male reindeer (Rangifer tarandus tarandus) calves in winter to investigate rumen function and digestion. Three calves were given S with 18.5% dry matter (DM), three were given SM (21.9% DM) and three were given H (85.0% DM). The content of water soluble carbohydrates (in % of DM) was 8.2% in S, 16.0% in SM and 8.5% in H. Median (range) daily DM food intake per kg BM was 12.9 (9-2-14.4) g in calves fed S, 19.0 (19-0-21.9) g in calves fed SM and 21.0 (19.2¬21.1) g in calves fed H. In vivo digestion of S and SM DM ranged from 78.5-83.1% compared to only 69-9-72.9% in calves fed H. In vitro DM digestion (IVDMD) of cellulose (median) incubated for 48 hours in rumen fluid was, however, significantly (F = 0.05) lower in calves fed S (24.4%) compared to calves fed SM (42.2%). Median IVDMD of cellulose (48 hours) in calves fed H was 36.4%. Total concentration of VFA (range) in the rumen fluid from reindeer fed H (99.7-113.6 mM) and was significantly (P<0.05) higher compared to animals fed S (57.7-85.9 mM) or SM (51.4-72.0 mM). Likewise, the pH of the rumen fluid (range) was significantly (P<0.05) lower in reindeer fed H (6.40-6.78) compared to animals fed S (6.97-7.30) or SM (6.79-7.27). Based on this study it is concluded that leafy timothy preserved as hay seems to be more suitable as emergency feed compared to silage. Supplementation of molasses to silage seems to stimulate food intake and ruminal cellulose digestion in reindeer. The lower intake of S compared to SM or H by reindeer may be explained by ruminal energy deficiency.

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Obestatin acts in brain to inhibit thirst

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00395.2006 ◽

2007 ◽

Vol 292 (1) ◽

pp. R637-R643 ◽

Cited By ~ 91

Author(s):

Willis K. Samson ◽

Meghan M. White ◽

Christopher Price ◽

Alastair V. Ferguson

Keyword(s):

Food Intake ◽

Pituitary Gland ◽

Behavioral Activity ◽

Free Access ◽

Gene Encoding ◽

Gh Secretion ◽

Water Drinking ◽

Access To Water

Derived from the same prohormone, obestatin has been reported to exert effects on food intake that oppose those of ghrelin. The obestatin receptor GPR39 is present in brain and pituitary gland. Since the gene encoding those two peptides is expressed also in those tissues, we examined further the possible actions of obestatin in vivo and in vitro. Intracerebroventricular administration of obestatin inhibited water drinking in ad libitum-fed and -watered rats, and in food-and water-deprived animals. The effects on water drinking preceded and were more pronounced than any effect on food intake, and did not appear to be the result of altered locomotor/behavioral activity. In addition, obestatin inhibited ANG II-induced water drinking in animals provided free access to water and food. Current-clamp recordings from cultured, subfornical organ neurons revealed significant effects of the peptide on membrane potential, suggesting this as a potential site of action. In pituitary cell cultures, log molar concentrations of obestatin ranging from 1.0 pM to 100 nM failed to alter basal growth hormone (GH) secretion. In addition, 100 nM obestatin failed to interfere with the stimulation of GH secretion by GH-releasing hormone or ghrelin and did not alter the inhibition by somatostatin in vitro. We conclude that obestatin does not act in pituitary gland to regulate GH secretion but may act in brain to alter thirst mechanisms. Importantly, in rats the effects of obestatin on food intake may be secondary to an action of the peptide to inhibit water drinking.

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Inhibition of Listeria monocytogenes by Lactobacillus plantarum is abolished by food intake, in an in vitro simulation of the pig colon

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200598160 ◽

1998 ◽

Vol 1998 ◽

pp. 164-164

Author(s):

K. Hillman ◽

R. Khaddour ◽

D. R. Fenlon

Keyword(s):

Escherichia Coli ◽

Listeria Monocytogenes ◽

Food Intake ◽

Lactobacillus Plantarum ◽

Enteric Pathogen ◽

Intestinal Health ◽

Microbial Cultures ◽

In Vitro Simulation ◽

Physiological Differences

Probiotics are live microbial cultures fed to animals with the intention of promoting intestinal health. However, one of the problems with these preparations is the variability in their effectiveness, reasons for which include genetic and physiological differences between herds of animals or between individuals, and the type of feed presented to the animals. This study has examined the effects of different food types on the efficacy of a strain of Lactobacillus plantarum as an inhibitor of Listeria monocytogenes. The strain of L. plantarum used (PF31) has been previously shown to inhibit the growth of the porcine enteric pathogen Escherichia coli O 149:K88:K91 in coculture (Hillman and Fox, 1994). In a subsequent series of tests, L. plantarum PF31 was also shown to inhibit the growth of List, monocytogenes in coculture.

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Effect of chronic ingestion of ethanol on in vitro uptake of lipids and glucose in the rabbit jejunum

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1984.246.2.g120 ◽

1984 ◽

Vol 246 (2) ◽

pp. G120-G129

Author(s):

A. B. Thomson

Keyword(s):

Fatty Acids ◽

Food Intake ◽

Weight Control ◽

Bulk Phase ◽

Unstirred Layer ◽

Control Group ◽

Cholesterol Uptake ◽

Incremental Change ◽

Rabbit Jejunum

This study was undertaken to determine the effect of chronic feeding of ethanol on the in vitro jejunal uptake of lipids and glucose. The first group of rabbits was fed ad libitum (CAL); the food intake of a second control group [weight control (WC)] was restricted to match their gain in body weight with that of a chronically ethanol-fed group (ETH); and the food intake of a third control group [food control (FC)] was restricted to match the food intake with that of ETH. There was a marked decline in cholesterol uptake in WC and FC compared with CAL, and cholesterol uptake in ETH was intermediate between the higher value in CAL and the lower value in WC and FC. The uptake of fatty acids 4:0-12:0 was similar in the CAL, FC, WC, and ETH groups, both when the bulk phase was stirred and unstirred; the uptake of fatty acids 16:0 and 18:0 was lower in WC and FC than in CAL; and the uptake of fatty acids 14:0, 16:0, and 18:0 was even lower in ETH. The uptake of a homologous series of fatty alcohols was greater in WC and ETH than in CAL at five different rates of stirring of the bulk phase. When the uptake of fatty acids 6:0-12:0 was corrected for unstirred layer resistance, a linear relation was noted between fatty acid chain length and the natural logarithm of rate of uptake/aqueous diffusion coefficient, and the steeper slope in WC and ETH than in CAL represented a higher incremental change in free energy. Glucose uptake was similar in CAL, WC, and FC but was greater in ETH from 5 to 40 mM glucose. These studies demonstrate that 1) weight restriction, food restriction, and chronic ethanol feeding are associated with a change in the effective resistance of the unstirred layer and in the passive permeability properties of the rabbit jejunum, and 2) ethanol has a differential effect on passive permeation of short-, medium-, and long-chain fatty acids and cholesterol.

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Inhibition of Listeria monocytogenes by Lactobacillus plantarum is abolished by food intake, in an in vitro simulation of the pig colon

Proceedings of the British Society of Animal Science ◽

10.1017/s0308229600033778 ◽

1998 ◽

Vol 1998 ◽

pp. 164-164

Author(s):

K. Hillman ◽

R. Khaddour ◽

D. R. Fenlon

Keyword(s):

Escherichia Coli ◽

Listeria Monocytogenes ◽

Food Intake ◽

Lactobacillus Plantarum ◽

Enteric Pathogen ◽

Intestinal Health ◽

Microbial Cultures ◽

In Vitro Simulation ◽

Physiological Differences

Probiotics are live microbial cultures fed to animals with the intention of promoting intestinal health. However, one of the problems with these preparations is the variability in their effectiveness, reasons for which include genetic and physiological differences between herds of animals or between individuals, and the type of feed presented to the animals. This study has examined the effects of different food types on the efficacy of a strain of Lactobacillus plantarum as an inhibitor of Listeria monocytogenes. The strain of L. plantarum used (PF31) has been previously shown to inhibit the growth of the porcine enteric pathogen Escherichia coli O 149:K88:K91 in coculture (Hillman and Fox, 1994). In a subsequent series of tests, L. plantarum PF31 was also shown to inhibit the growth of List, monocytogenes in coculture.

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Plasma membrane-specific deficiency in cardiac beta-adrenergic receptor in streptozocin-diabetic rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1989.257.2.e127 ◽

1989 ◽

Vol 257 (2) ◽

pp. E127-E132 ◽

Cited By ~ 3

Author(s):

A. Kashiwagi ◽

Y. Nishio ◽

Y. Saeki ◽

Y. Kida ◽

M. Kodama ◽

...

Keyword(s):

Cell Surface ◽

Adrenergic Receptor ◽

Insulin Treatment ◽

Diabetic Rats ◽

Cell Surface Receptor ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Receptor Concentration ◽

Cgp 12177

Cell surface [3H]CGP 12177 binding sites in 10-wk streptozocin-diabetic rats decreased by 41% (P less than 0.01) compared with that in the control rats. In contrast, there was no difference in the total cell receptor concentration between the control and the diabetic rats, which was measured by hydrophobic antagonist [125I]-iodocyanopindolol binding. Forty-eight-hour in vivo insulin treatment significantly (P less than 0.05) increased cell surface beta-adrenergic receptor concentration by 37% above that in diabetic rats without any change in total receptor concentration in the cells. However in vitro treatment of 8 nM insulin, 33 mM glucose, or 10 mM 3-hydroxybutyrate for 2 h showed no effect on [3H]CGP 12177 binding. In contrast, 10 microM isoproterenol-dependent decrease and the recovery of cell surface receptors after the removal of the agonist were significantly (P less than 0.01) impaired in diabetic rats compared with those of control rats. These results indicate that only cell surface beta-adrenergic receptors decrease in diabetic rats, which may be associated with abnormalities in the receptor distribution. The decrease in cell surface receptor number closely associates with the diabetic state and is reversed by the short-term insulin treatment.

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