Insulin Levels In Rats Research Articles

Effect of bromocriptine on cardiovascular complications associated with metabolic syndrome in fructose fed rats

Objective:The objective of the present study was to evaluate the effect of bromocriptine on cardiovascular complications associated with type-2 diabetes mellitus (DM).Materials and Methods:Metabolic syndrome or type 2 DM was induced by administration of fructose (66% solution, p.o.) in rats. Bromocriptine mesylate (10 mg/kg, i.p.) was given in fructose-treated rats for a period of 6 weeks after induction of diabetes. After drug treatment, the parameters such as body weight, food and water intake, serum glucose, triglycerides, cholesterol, insulin, and blood pressure (BP) were measured weekly and at the end of study. At the end of treatment, BP was determined by invasive method and vascular reactivity was tested with adrenaline (Adr), noradrenaline (NA), and phenylephrine (PE). Acetylcholine-induced vasorelaxation was tested on isolated rat aorta and histopathology of hearts was also done.Results:Fructose-fed rats showed significant weight gain, hyperglycemia, hyperlipidemia, hyperinsulinemia, and rise of BP. Administration of bromocriptine at a dose 10 mg/kg, i.p. significantly decreased weight gain, serum glucose, triglyceride, cholesterol and insulin levels in rats fed on fructose. Bromocriptine also significantly reduced elevated BP in fructose-fed hypertensive rats. Chronic treatment with bromocriptine significantly improved the relaxant response to acetylcholine on fructose-fed hyperinsulinemic rat aorta and also reduced the pressor response to Adr, NA, and PE. Bromocriptine also showed a protection from hypertrophy and degenerative changes in myocardium.Conclusion:Bromocriptine has beneficial effect in reduction of cardiovascular complications associated with metabolic syndrome.

The Involvement of Adenosine Triphosphate-Sensitive Potassium Channels in the Different Effects of Sevoflurane and Propofol on Glucose Metabolism in Fed Rats

Recently, we reported marked differences in the effects of sevoflurane and propofol on glucose metabolism; glucose use is impaired by sevoflurane, but not by propofol. Opening of adenosine triphosphate-sensitive potassium channels (K(ATP) channels) in β islet cells attenuates insulin secretion, while inhibition of K(ATP) channels in β islet cells increases insulin secretion. It is reported that volatile anesthetics open K(ATP) channels, whereas propofol inhibits K(ATP) channels. In this study, we examined the effects of sevoflurane and propofol on glucose metabolism under normovolemic and hypovolemic conditions, focusing on insulin secretion. Anesthesia was induced with sevoflurane (3% in 1 L/min oxygen) in all rats. After surgical preparation, rats were assigned to 2 groups. Anesthesia was maintained with sevoflurane (2% in 1 L/min oxygen) in the 1st group, and with propofol (a bolus dose of 30 mg/kg followed by continuous infusion at a rate of 30 mg · kg(-1) · h(-1)) in the 2nd group. Each group was divided into 3 subgroups: rats without pretreatment, rats pretreated with glibenclamide, and rats pretreated with nicorandil. After a 30-minute stabilization period, we withdrew 15 mL/kg of blood to induce hypovolemia. We evaluated glucose metabolism under both normovolemic and hypovolemic conditions by measuring blood glucose levels and plasma insulin levels. Under both normovolemia and hypovolemia, glucose levels in rats anesthetized with sevoflurane were significantly higher than those in rats anesthetized with propofol, and insulin levels in rats anesthetized with sevoflurane were significantly lower than those in rats anesthetized with propofol. Glibenclamide, a K(ATP) channel inhibitor, significantly decreased glucose levels and significantly increased insulin levels under sevoflurane anesthesia, suggesting that sevoflurane decreases insulin secretion by opening K(ATP) channels in β islet cells. Glibenclamide significantly decreased glucose levels and significantly increased insulin levels under propofol anesthesia as well; however, insulin levels in rats pretreated with glibenclamide under propofol anesthesia were much higher than those in rats pretreated with glibenclamide under sevoflurane anesthesia. Furthermore, insulin levels in rats without pretreatment under propofol anesthesia seemed to be equal to or higher than those in rats pretreated with glibenclamide under sevoflurane anesthesia. These results suggest that there are marked differences in the effects of sevoflurane and propofol on insulin secretion regulated by K(ATP) channels in β islet cells. Nicorandil, a K(ATP) channel opener, produced no significant effects on glucose metabolism under both sevoflurane and propofol anesthesia. Insulin secretion regulated by K(ATP) channels in β islet cells is involved, at least in part, in the different effects of sevoflurane and propofol on glucose metabolism.

Effects of Gosha-jinki-gan (Chinese herbal medicine: Niu-Che-SenQi-Wan) on hyperinsulinemia induced in rats fed a sucrose-rich diet

We investigated the effects of a Chinese herbal medicine, Gosha-jinki-gan (GJG), on the regulation of insulin levels in rats fed a sucrose-rich diet (SRD). Normal Wistar rats in the SRD group were fed an SRD for 4 weeks. Increased dietary sucrose did not alter plasma glucose levels but it increased plasma insulin levels at 2 and 4 weeks in the SRD-fed rats relative to control rats that were fed standard chow. GJG treatment significantly suppressed the SRD-induced elevation in plasma insulin levels. These results suggest that GJG improves hyperinsulinemia caused by an SRD.

Pioglitazone attenuates prostatic enlargement in diet‐induced insulin‐resistant rats by altering lipid distribution and hyperinsulinaemia

Increased incidence of benign prostatic hyperplasia among insulin-resistant individuals suggests a role for hyperinsulinaemia in prostatic enlargement. We have already reported increased cell proliferation and enlargement of prostate gland in insulin-resistant rats. The present study aimed to elucidate the molecular mechanisms underlying the reversal of prostatic enlargement in insulin-resistant rats by the peroxisome proliferator-activated receptor γ agonist pioglitazone. Sprague-Dawley rats were fed a normal pellet or a high-fat diet for 12 weeks with or without pioglitazone (20 mg·kg(-1)). Subgroups of animals fed different diets were castrated. Effects of dietary manipulation and pioglitazone were measured on insulin sensitivity, lipid distribution, cell proliferation and apoptosis. A high-fat diet led to the accumulation of fat in non-adipose tissues, insulin resistance, compensatory hyperinsulinaemia and prostatic enlargement in rats. Pioglitazone treatment altered fat distribution, improved insulin sensitivity and normalized lipid and insulin level in rats on the high-fat diet. The improved metabolic parameters led to decreased cellular proliferation and increased apoptosis in the prostate gland. High-fat diet feeding and pioglitazone treatment did not change plasma testosterone levels. However, significant prostatic atrophy was observed in castrated rats irrespective of dietary intervention. Our results show a previously unexplored therapeutic potential of pioglitazone for prostatic enlargement under insulin-resistant condition and further suggest that targeting distribution of lipid from non-adipose tissue to adipose tissue and insulin signalling could be new strategies for the treatment of benign prostatic hyperplasia.

Preventive effects of chronic exogenous growth hormone levels on diet-induced hepatic steatosis in rats.

BackgroundNon-alcoholic fatty liver disease (NAFLD), which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH) could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms.ResultsHigh-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha) levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin), which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways.ConclusionsChronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance.

Insulinostatic activity of cerebellin — Evidence from in vivo and in vitro studies in rats

Cerebellin (CER) is a neuromodulatory hexadecapeptide that originates from the precursor protein precerebellin (Cbln1). Four highly homologous isoforms of Cbln are known (Cbln1–Cbln4), which are expressed in the central nervous system (CNS) and in peripheral tissues. CER modulates synaptic structure formation in the CNS, whereas in the peripheral tissues CER regulates catecholamine secretion. Cbln is also expressed in the pancreas; however, its function in the pancreas is unknown. Here, we demonstrate the role of CER in regulating insulin secretion in vivo and in vitro. We identified Cbln1 and Cbln3 transcripts in rat pancreatic islets and detected Cbln-immunoreactivity, predominantly located in the periphery of the rat endocrine pancreas. In vivo, CER reduced plasma insulin levels in rats after 1 and 2 h. CER decreased insulin secretion from isolated rat pancreatic islets at high (11 mM), but not at low (3.33 mM) glucose concentration. CER inhibited stimulated insulin secretion from clonal rat insulinoma (INS-1) cells, reduced forskolin-induced production of cAMP and intracellular calcium concentration. Our study demonstrates for the first time that Cbln1 and Cbln3 are expressed in the rat endocrine pancreas. Furthermore, we identify CER as an insulinostatic factor, which decreases intracellular cAMP production and calcium in INS-1 cells.

Cinchonain Ib isolated from Eriobotrya japonica induces insulin secretion in vitro and in vivo

Aims of the study Eriobotrya japonica leaves had been used traditionally for the treatment of diabetes mellitus by immersing the dried leaves in a hot water drink. Few studies have shown the hypoglycemic effect of Eriobotrya japonica using crude alcoholic extract and isolated methanolic compounds. These studies proposed that the mechanism of action could be by stimulating the β-islets of Langerhans to secrete insulin, however with no scientific evidence. Methods Eriobotrya japonica water extract (EJWE) and the compounds derived from it: cinchonain Ib, procyanidin B-2, chlorogenic acid and epicatechin, were tested for their effects on insulin secretion from INS-1 cells and following oral administration in rats. Results The present study showed that EJWE increased significantly ( p < 0.05) insulin secretion from INS-1 cells in dose-dependent manner. Oral administration of EJWE at 230 mg/kg to rats, however, decreased plasma insulin level for as long as 240 min post-administration and caused a transient drop of blood glucose at 15 and 30 min post-administration. On the other hand, cinchonain Ib enhanced significantly ( p < 0.05) insulin secretion from INS-1 cells, whereas epicatechin inhibited significantly ( p < 0.05) insulin secretion from INS-1 cells. In addition, cinchonain Ib enhanced significantly (150%: p < 0.05) plasma insulin level in rats for as long as 240 min after 108 mg/kg oral administration but did not induce any change in blood glucose level. Conclusion These data indicate that cinchonain Ib has an insulinotropic effect and suggest the possible use of cinchonain Ib for managing type 2 diabetes.

Circadian changes of d-alanine and related compounds in rats and the effect of restricted feeding on their amounts

The circadian changes of d-alanine ( d-Ala), an intrinsic d-amino acid found in mammals, were investigated in rats with diurnal and nocturnal habits, and the profiles were compared to those of l-Ala, other d-amino acids and several hormones. Determination of d-Ala in the rat plasma, pancreas and anterior pituitary gland was carried out using a sensitive and selective two-dimensional HPLC system combining a micro-ODS column and an enantioselective column after fluorescence derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F). The amount of d-Ala was high during the sleeping period and low during the active period in rats with both diurnal and nocturnal habits, indicating for the first time that the d-Ala is closely related to the activity rhythm of animals. In contrast, l-Ala and other d-amino acids did not show any clear circadian changes. The circadian change of d-Ala inversely correlated with that of the plasma insulin level in rats with both diurnal and nocturnal habits. Considered together with our previous findings that d-Ala is localized in the insulin secreting beta-cells in the rat pancreas, it is strongly suggested that d-Ala has some functional relationships to insulin in mammals.

Influence of Tacrolimus and Ciprofloxacin on Glucose Metabolism

Tacrolimus is an immunosuppressive drug that causes glucose intolerance. On the other hand, ciprofloxacin, which is widely used in the treatment of infectious diseases, is known to cause hypoglycemia as a side effect. We investigated the effects of tacrolimus and ciprofloxacin on serum glucose and insulin levels in rats, as well as on insulin secretion and the viability of HIT-T15 cells. The rats received intraperitoneal injections of tacrolimus and/or ciprofloxacin for 1 week, and their arterial blood was sampled after the administration of glucose. HIT-T15 cells were cultured in the presence of tacrolimus and/or ciprofloxacin, and the insulin level in the supernatant was measured. Ciprofloxacin did not show a significant effect on serum glucose and insulin levels after multiple administrations in the rats. In contrast, rats in the tacrolimus treatment group showed low serum insulin and high serum glucose levels. Moreover, the coadministration of ciprofloxacin and tacrolimus resulted in higher glucose levels compared with tacrolimus alone 0.5 h after glucose stimulation. In addition, we observed that the rats administered tacrolimus and/or ciprofloxacin had low body weight and food intake. Tacrolimus caused a dose-dependent decrease in the viability of the HIT-T15 cells. Furthermore, both drugs were highly toxic to HIT-T15 cells. In contrast, tacrolimus alone and coadministration of the drugs resulted in no significant difference in insulin secretion. These results suggest that the cytotoxic effects of ciprofloxacin and tacrolimus cause a decrease in insulin secretion, leading to glucose intolerance.

Rectangular cymbal arrays for improved ultrasonic transdermal insulin delivery

Circular cymbal ultrasound arrays have been shown to be effective in delivering therapeutic levels of insulin in rats, rabbits, and pigs. To improve delivery efficiency, a rectangular cymbal design was desired in order to achieve a broader spatial intensity field without increasing the size of the device or the spatial-peak temporal-peak intensity (I(SPTP)). With a similar intensity (50 mWcm(2)), the goal was to determine if the 3x1 rectangular cymbal array could perform significantly better than the 3x3 circular array for glucose reduction in hyperglycemic rabbits. Rabbit experiments were performed using three groups: nonsonicated control (n=3), ultrasound exposure using a circular cymbal array (n=3), and ultrasound exposure using a rectangular cymbal array (n=3). Rabbits were anesthetized and a water tight reservoir that held the insulin was fastened on the rabbit's thigh. At the beginning of the experiment and every 15 min for 90 min, the blood glucose level was determined. For comparison between individual rabbits, the absolute level is normalized by subtracting out the baseline in order to arrive at the change in glucose level. For the control group, the normalized glucose level increased (more hyperglycemic) to +80.0+/-28.8 mgdl (mean+/-SEM). Using the circular array, the glucose level decreased to -146.7+/-17.8 mgdl at 90 min. However, using the rectangular cymbal array, the glucose decreased faster and to a level of -200.8+/-5.9 mgdl after 90 min. These results indicated the feasibility of the rectangular cymbal array as an improved device for drug delivery.

Effect of cerebrocrast, a new long‐acting compound on blood glucose and insulin levels in rats when administered before and after STZ‐induced diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by selective destruction of insulin secreting pancreatic islets beta-cells. The formation of cytokines (IL-1beta, IL-6, TNF-alpha, etc.) leads to extensive morphological damage of beta-cells, DNA fragmentation, decrease of glucose oxidation, impaired glucose-insulin secretion and decreased insulin action and proinsulin biosynthesis. We examined the protective effect of a 1,4-dihydropyridine (DHP) derivative cerebrocrast (synthesized in the Latvian Institute of Organic Synthesis) on pancreatic beta-cells in rats possessing diabetes induced with the autoimmunogenic compound streptozotocin (STZ). Cerebrocrast administration at doses of 0.05 and 0.5 mg/kg body weight (p.o.) 1 h or 3 days prior to STZ as well as at 24 and 48 h after STZ administration partially prevented pancreatic beta-cells from the toxic effects of STZ, and delayed the development of hyperglycaemia. Administration of cerebrocrast starting 48 h after STZ-induced diabetes in rats for 3 consecutive days at doses of 0.05 and 0.5 mg/kg body weight (p.o.) significantly decreased blood glucose level, and the effect remained 10 days after the last administration. Moreover, in these rats, cerebrocrast evoked an increase of serum immunoreactive insulin (IRI) level during 7 diabetic days as compared to both the control normal rats and the STZ-induced diabetic control rats. The STZ-induced diabetic rats that received cerebrocrast had a significantly high serum IRI level from the 14th to 21st diabetic days in comparison with the STZ-induced diabetic control. The IRI level in serum as well as the glucose disposal rate were significantly increased after stimulation of pancreatic beta-cells with glucose in normal rats that received cerebrocrast, administered 60 min before glucose. Glucose disposal rate in STZ-induced diabetic rats as a result of cerebrocrast administration was also increased in comparison with STZ-diabetic control rats. Administration of cerebrocrast in combination with insulin intensified the effect of insulin. The hypoglycaemic effect of cerebrocrast primarily can be explained by its immunomodulative properties. Moreover, cerebrocrast can act through extrapancreatic mechanisms that favour the expression of glucose transporters, de novo insulin receptors formation in several cell membranes as well as glucose uptake.

Antidiabetic effect ofCinnamomum cassia andCinnamomum zeylanicum In vivo andIn vitro

Rats were given Cinnamomum cassia bark or extracts from Cinnamomum cassia and zeylanicum to evaluate blood glucose and plasma insulin levels in rats under various conditions. The cassia extract was superior to the zeylanicum extract. The cassia extract was slightly more efficacious than the equivalent amount of Cassia bark. A decrease in blood glucose levels was observed in a glucose tolerance test (GTT), whereas it was not obvious in rats that were not challenged by a glucose load. The elevation in plasma insulin was direct since a stimulatory in vitro effect of insulin release from INS-1 cells (an insulin secreting cell line) was observed. Thus the cassia extract has a direct antidiabetic potency.

Circulating adiponectin levels increase in rats on caloric restriction: the potential for insulin sensitization

Caloric restriction (CR) has a well-known insulin sensitizing effect in vivo. Although this effect has been confirmed in rodents and primates for many years, its precise molecular mechanisms remain unknown. Here we show a significant increase in plasma adiponectin and a decrease in blood glucose, plasma triglyceride and insulin levels in rats maintained on CR diet for 2, 10, 15, and 20 months. Long-term CR rats exhibited significantly higher insulin-stimulated insulin receptor tyrosine phosphorylation and lower PTP-1B activity both in liver and skeletal muscle than those observed in rats fed ad libitum (AL). In addition, the triglyceride levels in these tissues were significantly lower in long-term CR animals. Interestingly, concentrations of plasma adiponectin in long-term CR rats were associated with increased expression of the transcription factor mRNAs for the peroxisome proliferator-activated receptor (PPAR)α, γ and δ, but decreased expression for SREBP-1c, resulting in a concerted modulation in the expression of key transcription target genes involved in fatty acid oxidation and energy combustion in liver. Taken together, our findings suggest an important role for adiponectin in the beneficial effects of long-term CR.

ペントース関連物質および糖アルコールの栄養特異性

A recent trend has been to use commonly available foods in the prevention of disease. Such application is dependent on a food chemical and physical composition. We investigated functional ac tivity of substances derived from pentose when given in combination with various saccharides to rats. We observed that pentose-derivatives (fructosylxylosides, xylitol, some nucleosides) had a sup pressive effect on the elevation of blood glucose and insulin levels in rats given sucrose or soluble starch. The effect was due to the inhibition of disaccharide hydrolases. We also found that fructo sylxylosides and adenosine enhanced mineral (calcium and magnesium) absorption when given in combination with sucrose.

Acute effect of growth hormone to induce peripheral insulin resistance is independent of FFA and insulin levels in rats.

To examine whether growth hormone (GH) induces peripheral insulin resistance by altering plasma free fatty acid (FFA) or insulin levels, the effects of GH infusion on insulin-stimulated glucose fluxes were studied in conscious rats under two protocols. In study 1, either saline (n = 7) or human recombinant GH (21 microg. kg(-1). h(-1); n = 8) was infused for 300 min, and insulin-stimulated glucose fluxes were estimated during the final 150-min period of hyperinsulinemic euglycemic clamps. In study 2, hyperinsulinemic euglycemic clamps were first conducted for 150 min (to raise plasma insulin and suppress FFA levels), and saline or GH (n = 7 for each) was subsequently infused for the following 300-min clamp period. In study 1, GH infusion in the basal state did not significantly alter plasma FFA or insulin levels. In contrast, GH infusion decreased insulin-stimulated glucose uptake, glycolysis, and glycogen synthesis by 32, 27, and 40%, respectively (P < 0.05). In study 2, GH infusion during hyperinsulinemic euglycemic clamps did not alter plasma FFA or insulin levels (P > 0.05). GH infusion had no effect on insulin-stimulated glucose uptake during the initial 150 min but eventually decreased insulin-stimulated glucose uptake by 37% (P < 0. 05), similar to the results in study 1. These data indicate that GH induces peripheral insulin resistance independent of plasma FFA and insulin levels. The induction of insulin resistance was preceded by suppression of glycogen synthesis, consistent with the hypothesis that metabolic impairment precedes and causes development of peripheral insulin resistance.

Repaglinide, a new oral antidiabetic agent: a review of recent preclinical studies.

Repaglinide is a new carbamoylmethyl benzoic acid derivative that is structurally related to meglitinide. In common with all active oral hypoglycaemic agents, it displays a comparable U-shaped configuration. Repaglinide exerts its effects by binding to a site on the plasma membrane of beta-cells, thereby closing ATP-sensitive potassium channels. This causes depolarization of the beta-cell and the opening of voltage-sensitive calcium channels allowing the influx of extracellular calcium ions. This increase in intracellular calcium, in turn, stimulates insulin release. The insulinotropic effect of repaglinide is not related to its ionophoretic capacity. Repaglinide does not cause insulin release in the absence of exogenous glucose, nor does it inhibit the biosynthesis of proinsulin. In vivo administration of an ester of succinic acid potentiates the insulin secretory response to concomitantly administered repaglinide. Repaglinide causes a more rapid increase in plasma insulin levels in rats than either glibenclamide or glimepiride.

Inhibition of Insulin Release by Intraduodenally Infused Enterostatin-VPDPR in Rats

Mei, J., M. Bouras and C. Erlanson-Albertsson. Inhibition of insulin release by intraduodenally infused enterostatin-VPDPR in rats. Peptides 18(5) 651–655, 1997.—Enterostatin, an amino-terminal pentapeptide produced in the intestinal lumen after cleavage of pancreatic procolipase, has been shown to suppress fat intake in rats after intraduodenal infusion. In this study, female Sprague-Dawley rats fitted with a duodenal catheter were intestinally infused with enterostatin (Val-Pro-Asp-Pro-Arg, 11.3 and 22.6 nmol/kg/min) plus 20% Intralipid for 30 min. Plasma insulin levels were significantly reduced, whereas plasma glucose concentrations were not altered by enterostatin-VPDPR. The tripeptide Asp-Pro-Arg was also found to decrease the levels of plasma insulin. However, the pentapeptide with the sequence Val-Pro-Gly-Pro-Arg, des-Arg-enterostatin Val-Pro-Asp-Pro and the tripeptide Pro-Asp-Pro failed to cause the reduction of plasma insulin levels in rats following intestinal infusion of these peptides. Radiolabeled enterostatin ([3H]VPDPR) was identified in plasma by HPLC following intraduodenal infusion of the peptide, indicating that the appearance of an intact enterostatin-VPDPR in blood. It is concluded that intestinally administered enterostatin-VPDPR and its metabolites reduce plasma levels of insulin stimulated by Intralipid.

Dietary fish oil normalize dyslipidemia and glucose intolerance with unchanged insulin levels in rats fed a high sucrose diet

The aim of this study was to investigate the relationship between the lipid-lowering effects of fish oils and concomitant consequences on glucose tolerance and insulin sensitivity in an experimental animal model of hypertriglyceridemia induced by high sucrose intake. To achieve this goal, male Wistar rats were fed a semi-synthetic sucrose rich diet (SRD) (w/w: 62.3% sucrose, 8% corn oil, 17% protein) for 90 days. At the time, a well established and permanent hypertriglyceridemia accompanied by glucose intolerance was present. After that, one half of the animals continued on the SRD up to 120 days. The other half received an SRD in which the source of fat was substituted by cod liver oil (w/w 7% CLO plus 1% corn oil) from day 90 to 120 (SRD + CLO). Control rats were fed a semi-synthetic diet (CD) (w/w: 62.5% corn starch, 8% corn oil, 17% protein) throughout the 120 days experimental period. Results obtained after the experimental period show that the hypertriglyceridemia and glucose intolerance ensuing long term feeding normal rats with a sucrose-rich diet could be completely reversed mediating no change in circulating insulin levels by shifting the source of fat in the diet from corn oil to cod liver oil. These findings suggest that manipulation of dietary fats may play a role in the management of the lipid disorders associated with glucose intolerance and insulin resistance.

Diet cycling and age alter weight gain and insulin levels in rats

For assessment of the effect of diet cycling on body weight gain patterns, 3-mo-old male Sprague-Dawley rats were either cycled from chow to a high-energy condensed milk (CM) diet, back to chow, and then back to CM diet at 3-mo intervals (cyclers) or were fed chow to 9 mo of age and then CM diet for 3 mo (noncyclers). Nine of 21 cyclers developed diet-induced obesity (DIO), gaining 36, 59, and 281% more weight than chow-fed controls (CF) at each cycle, respectively. Twelve cycled rats were diet-resistant (DR) with comparable weight gain to CF rats after the first CM diet and chow cycles. However, they gained 202% more than CF rats and 50% more, with 29% heavier retroperitoneal fat pads, than noncycled DR rats after their second CM diet cycle begun at 9 mo of age. Enhanced weight gain in DR cyclers was probably due to enhanced food efficiency in the last few weeks of CM diet intake. Plasma insulin levels were 70% higher in cycled vs. noncycled DIO and DR rats, and both were higher than CF rats. Unlike 6-mo-old DR rats in a prior study, 12-mo-old noncycled DR rats after 3 mo on CM diet here had 45-172% higher alpha 2-adrenoceptors binding in 6 of 17 brain areas than noncycled DIO and/or CF rats. Thus age, diet cycling, and brain alpha 2-adrenoceptors interact to affect long-term changes in weight gain and metabolism.

Indications of pre- and post-synaptic 5-HT 1A receptor interactions in feeding behavior and neuroendocrine regulation

This bipartite study uses behavioral and biochemical means to explore the involvement of both pre- and post-synaptic 5-HT 1A receptors in the control of food intake and neuroendocrine regulation. In the pharmacological study, the administration of the 5-HT 1A receptor agonist 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT; 60 μg/kg b.wt., i.p.) to rats caused a significant increase in 2 h intake of a high carbohydrate (CARB)/sugar diet ( P < 0.05) during the relatively inactive feeding period of the late light cycle. No significant change was detected in the intake of Purina laboratory chow at 2 h, or of the intake of either diet at 4 h and 24 h after 8-OH-DPAT administration. Injection of 8-OH-DPAT induced a drop in insulin levels in rats maintained on high CARB/sugar diets only (−90%; P<0.05). It also caused an increase in circulating glucose levels in both high CARB/sugar (240%; P<0.01) and chow fed (123%; P<0.05) rats; it did so more intensely in high CARB/sugar-fed rats. In the biochemical study, radioligand binding techniques were used to assess 5-HT 1A receptor density in the hypothalamus, as well as the relationship between 5-HT 1A receptors and circulating levels of insulin and glucose. Chronic and acute administration (25 mg/kg b.wt./5 injections, and 50 mg/kg b.wt., respectively, i.p.) of the potent hypoglyce mic agent tolbutamide (TOL) caused a significant increase in 5-HT 1A receptor density (+243% and +132.6%, respectively; P<0.05) in the medial hypothalamus but not in the lateral hypothalamus, as compared to vehicle-treated rats. Chronic glucose replacement therapy showed a trend towards reversing the depressed circulating glucose levels as well as the medial hypothalamic 5-HT 1A receptor density to control levels. These studies indicate that the pre-synaptic mechanism of 8-OH-DPAT-induced hyperphagia may require specific circulating levels of insulin and glucose, which are regulated via post-synaptic 5-HT 1A receptors.