Significant Increase In Insulin Research Articles

Shifts in metabolic parameters surrounding glucose homoeostasis resulting from tricyclic antidepressant therapy: implications of insulin resistance?

This study displayed the physiological effects the tricyclic antidepressants amitriptyline or trimipramine have on glucose homoeostasis in male Wistar rats. An insulin secreting cell line (INS-1) was also used to determine effects tricyclic antidepressants have on insulin secretion and insulin displacement. Thirty rats each received a 1 mg kg-1 dose of amitriptyline or trimipramine for a period of 14 weeks; another 14 rats served as the control group. Blood glucose, serum insulin and muscle and liver glycogen levels were determined. Kidney, liver and muscle insulin degradation was measured and compared with insulin degrading enzyme concentrations in the latter two tissues. INS-1 cells were used to determine the effect 1 microM amitriptyline has on insulin secretion. Displacement studies for [3H]glibenclamide by amitriptyline or trimipramine were undertaken on INS-1 cells. A significant increase in blood glucose (P<0.01) was found for both test groups after 6 and 14 weeks of receiving the medication, which may be related to a significant decrease in liver and muscle glycogen levels (P<0.001). Serum insulin levels remained unchanged, although a significant increase in insulin degradation was observed in the muscle, liver and kidney, which may be related to a significant increase in insulin degrading enzyme (P<0.001) that was found. A significant increase in insulin secretion was observed for the INS-1 cells treated with amitriptyline, although no significant displacement for the [3H]glibenclamide was evident for amitriptyline or trimipramine. The significant alterations in glucose homoeostasis observed, as well as the significant changes associated with insulin secretion and degradation associated with amitriptyline or trimipramine treatment, imply that prolonged use of these medicines may lead to insulin resistance and full blown diabetes.

Effects of three antidiabetics on insulin and leptin in Chinese type 2 diabetes

Aims This study was to investigate the effects of some different antidiabetics on circulating insulin and leptin levels in type 2 diabetes with or without overweight in a Chinese population. Methods 80 type 2 diabetes men with overweight (body mass index BMI > 24 kg/m 2) and 35 type 2 diabetes men with normal body weight (BMI ≤ 24 kg/m 2) and 56 control subjects were enrolled in the study. We measured blood glucose, insulin, leptin, total cholesterol, LDL-C, HDL-C, triglycerides, fasting glucose, postprandial glycose, HbA1c and BMI before and after the administration of antidiabetic drugs. Results Compared with normal body weight, the levels of plasma insulin and leptin in overweight type 2 diabetes men were higher, after 3 months treatment, a significant increase in insulin and leptin levels was observed in overweight type 2 diabetes men in gliclazide group. Levels of leptin and insulin decreased in metformin and rosiglitazone groups, respectively. Conclusions We conclude that surfonylureas treatment leads to increased insulin and leptin levels in overweight type 2 diabetes men, metformin, or rosiglitazone treatment can reduce insulin and leptin levels, respectively, and effect of metformin on plasma leptin and insulin levels is more significant than that of rosiglitazone.

Role of insulin, insulin‐like growth factor‐1, hyperglycaemic food and milk consumption in the pathogenesis of acne vulgaris

It is the purpose of this viewpoint article to delineate the regulatory network of growth hormone (GH), insulin, and insulin-like growth factor-1 (IGF-1) signalling during puberty, associated hormonal changes in adrenal and gonadal androgen metabolism, and the impact of dietary factors and smoking involved in the pathogenesis of acne. The key regulator IGF-1 rises during puberty by the action of increased GH secretion and correlates well with the clinical course of acne. In acne patients, associations between serum levels of IGF-1, dehydroepiandrosterone sulphate, dihydrotestosterone, acne lesion counts and facial sebum secretion rate have been reported. IGF-1 stimulates 5alpha-reductase, adrenal and gonadal androgen synthesis, androgen receptor signal transduction, sebocyte proliferation and lipogenesis. Milk consumption results in a significant increase in insulin and IGF-1 serum levels comparable with high glycaemic food. Insulin induces hepatic IGF-1 secretion, and both hormones amplify the stimulatory effect of GH on sebocytes and augment mitogenic downstream signalling pathways of insulin receptors, IGF-1 receptor and fibroblast growth factor receptor-2b. Acne is proposed to be an IGF-1-mediated disease, modified by diets and smoking increasing insulin/IGF1-signalling. Metformin treatment, and diets low in milk protein content and glycaemic index reduce increased IGF-1 signalling. Persistent acne in adulthood with high IGF-1 levels may be considered as an indicator for increased risk of cancer, which may require appropriate dietary intervention as well as treatment with insulin-sensitizing agents.

Concomitant Down Regulation of Glycolytic Enzymes, Upregulation of Gluconeogenic Enzymes and Potential Hepato-Nephro-Protective Effects Following the Chronic Administration of the Hypoglycemic, Insulinotropic Citrullus colocynthis Pulp Extract

Background Citrullus colocynthis pulp seedless extract has been demonstrated to have antihyperglycemic and insulinotropic effects. Problem statement: The mechanism(s) underlying the antihyperglycemic and insulinotropic effects have not been investigated to date. Approach: The influence of Citrullus colocynthis pulp extract administered orally was studied in alloxan diabetic white albino rats. Rats were divided into four groups, the first group was normal non diabetic rats given normal saline orally and was named control group, the second group was diabetic rats given normal saline orally and were named normal saline treated-diabetic rats, the third and fourth group were diabetic rats treated with the pulp extract or glybenclamide (a positive control) orally. Plasma glucose, glycosylated hemoglobin and insulin were determined in all groups. The effect of pulp extract of this plant on liver and kidney tissues was also studied. The amount of insulin in β-cells of the Islets of Langerhans in all groups was assessed using immunohistochemistry procedure. Results: Treatment of diabetic rats with Citrullus colocynthis pulp extract (300 mg kg-1 body weight) resulted in a significant decrease in plasma glucose, glygosylated Hb and increased insulin levels. This significant increase in insulin may explain the increase in the activity of liver hexokinase, with concomitant decrease of glucose 6-phosphatase and fructose-1,6-bisphosphatase. Immunohistochemistry procedure showed that the amount of insulin in β-cells of the islets of Langerhans is greater in Citrullus colocynthis treated-diabetic rats in comparison to non-treated diabetic rats. Conclusion: The present study clearly demonstrated that the folk medicinal plant Citrullus colocynthis pulp extract possesses a hypoglycemic effect, through an increase in insulin production and the subsequent increase in activity of glycolytic enzyme and decrease in activity of enzymes of gluconeogenesis. The present study also showed that the pulp extract of this plant to may have protective effects on the liver and kidney.

Therapeutic effects of Nigella sativa on chronic HAART-induced hyperinsulinemia in ratsThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 2 of a 2-part Special Issue).

Prolonged use of highly active antiretroviral therapy (HAART) is associated with insulin resistance in HIV-1-positive patients. Small animal models that recapitulate the long-term effects of HAART may facilitate the identification of therapeutic agents to suppress these side effects. We investigated the protective effects of black seed oil (BSO) from Nigella sativa in Sprague-Dawley rats treated with a daily HAART regimen for 7 months. The antiretroviral drugs, consisting of nelfinavir (200 mg/kg), zidovudine (50 mg/kg), and efavirenz (20 mg/kg), were mixed with diet with or without BSO (400 microL/kg) supplementation. Significant increases in insulin and C-peptide levels were observed in HAART-treated groups, and concomitant BSO treatment reduced this hyperinsulinemia. Interestingly, HAART-treated rats showed reduced size of pancreatic islets that was not seen in BSO-exposed rats. In vitro studies showed that nelfinavir, alone and in combination with HAART, induced oxidative stress and decreased glucose-induced insulin production in INS-1 cells. Suppressed insulin production was restored in cells coexposed to either BSO or thymoquinone. Our findings demonstrated that chronic HAART may increase serum insulin levels by dysregulating both insulin production by beta cells and insulin action at the periphery. These deleterious effects may be prevented by dietary supplementation with BSO.

A1adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents

There is substantial evidence in the literature that elevated plasma free fatty acids (FFA) play a role in the pathogenesis of type 2 diabetes. CVT-3619 is a selective partial A(1) adenosine receptor agonist that inhibits lipolysis and lowers circulating FFA. The present study was undertaken to determine the effect of CVT-3619 on insulin resistance induced by high-fat (HF) diet in rodents. HF diet feeding to rats for 2 wk caused a significant increase in insulin, FFA, and triglyceride (TG) concentrations compared with rats fed chow. CVT-3619 (1 mg/kg) caused a time-dependent decrease in fasting insulin, FFA, and TG concentrations. Acute administration of CVT-3619 significantly lowered the insulin response, whereas glucose response was not different with an oral glucose tolerance test. Treatment with CVT-3619 for 2 wk resulted in significant lowering of FFA, TG, and insulin concentrations in rats on HF diet. To determine the effect of CVT-3619 on insulin sensitivity, hyperinsulinemic euglycemic clamp studies were performed in C57BL/J6 mice fed HF diet for 12 wk. Glucose infusion rate was decreased significantly in HF mice compared with chow-fed mice. CVT-3619 treatment 15 min prior to the clamp study significantly (P < 0.01) increased glucose infusion rate to values similar to that for chow-fed mice. In conclusion, CVT-3619 treatment lowers FFA and TG concentrations and improves insulin sensitivity in rodent models of insulin resistance.

Differentiation of Embryonic Stem Cells Conditionally Expressing Neurogenin 3

Expression of the proendocrine gene neurogenin 3 (Ngn3) is required for the development of pancreatic islets. To better characterize the molecular events regulated by Ngn3 during development, we have determined the expression profiles of murine embryonic stem cells (mESCs) uniformly induced to overexpress Ngn3. An mESC line was created in order to induce Ngn3 by adding doxycycline to the culture medium. Genome-wide microarray analysis was performed to identify genes regulated by Ngn3 in a variety of contexts, including undifferentiated ESCs and differentiating embryoid bodies (EBs). Genes regulated by Ngn3 in a context-independent manner were identified and analyzed using systematic gene ontology tools. This analysis revealed Notch signaling as the most significantly regulated signaling pathway (p = .009). This result is consistent with the hypothesis that Ngn3 expression makes the cell competent for Notch signaling to be activated and, conversely, more sensitive to Notch signaling inhibition. Indeed, EBs induced to express Ngn3 were significantly more sensitive to gamma-secretase inhibitor-mediated Notch signaling inhibition (p < .0001) when compared with uninduced EBs. Moreover, we find that Ngn3 induction in differentiating ESCs results in significant increases in insulin, glucagon, and somatostatin expression.

The impact of 3-year changes in lifestyle habits on metabolic syndrome parameters: the D.E.S.I.R Study

The effect of lifestyle changes in cohorts of free-living populations has been surprisingly little evaluated. A longitudinal study. In the French Data from an Epidemiological Study on the Insulin Resistance (D.E.S.I.R) study of 1958 men and 2028 women, aged 30-65 years, the impact of 3-year changes in lifestyle habits (sporting activity, physical activity at home and at work, alcohol drinking, smoking) on metabolic syndrome parameters [insulin, glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, systolic blood pressure, waist circumference] and on body mass index (BMI) were investigated. In men, 3-year increases in sporting activity were associated with a lowering of insulin, glucose, systolic blood pressure and waist circumference (all P < 0.05). For women, the only effect was on lowering waist circumference (P < 0.03). Increases in physical activity at home were beneficially associated with HDL-cholesterol, triglycerides, waist circumference and BMI changes (all P < 0.05) in men, but had no apparent effect in women. Decreases in alcohol intake only had an effect in men, with decreases in HDL-cholesterol and systolic blood pressure (P < 0.05), whereas decreasing cigarette smoking in men was associated with significant increases in insulin, glucose, triglycerides, waist and BMI (P < 0.001), and in women HDL-cholesterol, waist circumference and BMI increased (P < 0.02). These results were mainly caused by those who had stopped smoking. Increases in physical activity over the 3-year period were associated with beneficial effects on syndrome parameters, particularly in men. Smoking cessation and alcohol moderation produced mixed effects on these parameters.

Endothelial Vasomotor Function In Women Assessed By Flow-mediated Dilation Before And After A High-fat Meal

Endothelial function is emerging as a surrogate marker for cardiovascular health and may be assessed using a non-invasive technique that employs increased flow and shear stress as a stimulus for brachial artery dilation. Flow-mediated dilation (FMD) is dependent on a healthy endothelium and the production and release of nitric oxide. In the presence of risk factors for CHD, for example chronic hyperlipidemia, FMD is attenuated. Acute hyperlipidemia, elicited by the ingestion of a high-fat meal has also been shown to impair FMD in healthy individuals for several hours. The resultant dysfunction may be due to increased levels of oxidative stress, suggesting that substances with antioxidant properties may protect against postprandial dysfunction. Estrogen has been shown to affect the endothelium causing the rapid release of nitric oxide. Estrogen may also have antioxidant properties. PURPOSE To test the hypothesis that postmenopausal women without hormone therapy would display impaired FMD following a high-fat meal and premenopausal women with endogenous estrogen, along with postmenopausal women with exogenous estrogen, would not display impaired FMD. METHODS Thirty healthy women were studied, 9 premenopausal, 10 postmenopausal with no hormone supplementation and 11 were postmenopausal taking hormone replacement therapy. FMD was measured following 4.5-mins of arterial occlusion including 1-minute of handgrip exercise after a 12-hour fast and again 3-hours after the ingestion of a high-fat meal (1018kcal, 56g of fat). RESULTS Following the high-fat meal FMD remained unaltered (9.39 ± 0.73 vs. 9.75 ± .0.64%, 8.71 ± 0.86 vs. 8.79 ± 0.79%, 9.80 ± 1.16 vs. 9.73 ± 1.06%, p<0.05) despite a significant increase in plasma TG levels (1.11 ± 0.2 vs. 1.91 ± 0.26mmol/L, 1.17 ± 0.15 vs. 1.86 ± 0.28mmol/L, 1.22 ± 0.24 vs. 1.78 ± 0.26mmol/L, p<0.0001 for premenopausal, postmenopausal and hormone replacement groups respectively). The high-fat meal also elicited a significant increase in insulin (9.45 ± 1.34 vs. 39.10 ± 11.32 ± μIU/ml, 8.89 ± 1.17 vs. 32.39 ± 3.17μIU/ml, 7.80 ± 0.81 vs. 32.63 vs. 4.77μIU/ml, p<0.0001). CONCLUSIONS Preserved FMD after a high-fat meal in this study may be explained by the use of healthy active women. Supported by NSERC Canada and the Heart and Stroke Foundation of ON, Canada

Endothelial Vasomotor Function In Women Assessed By Flow-mediated Dilation Before And After A High-fat Meal

Endothelial function is emerging as a surrogate marker for cardiovascular health and may be assessed using a non-invasive technique that employs increased flow and shear stress as a stimulus for brachial artery dilation. Flow-mediated dilation (FMD) is dependent on a healthy endothelium and the production and release of nitric oxide. In the presence of risk factors for CHD, for example chronic hyperlipidemia, FMD is attenuated. Acute hyperlipidemia, elicited by the ingestion of a high-fat meal has also been shown to impair FMD in healthy individuals for several hours. The resultant dysfunction may be due to increased levels of oxidative stress, suggesting that substances with antioxidant properties may protect against postprandial dysfunction. Estrogen has been shown to affect the endothelium causing the rapid release of nitric oxide. Estrogen may also have antioxidant properties. PURPOSE To test the hypothesis that postmenopausal women without hormone therapy would display impaired FMD following a high-fat meal and premenopausal women with endogenous estrogen, along with postmenopausal women with exogenous estrogen, would not display impaired FMD. METHODS Thirty healthy women were studied, 9 premenopausal, 10 postmenopausal with no hormone supplementation and 11 were postmenopausal taking hormone replacement therapy. FMD was measured following 4.5-mins of arterial occlusion including 1-minute of handgrip exercise after a 12-hour fast and again 3-hours after the ingestion of a high-fat meal (1018kcal, 56g of fat). RESULTS Following the high-fat meal FMD remained unaltered (9.39 ± 0.73 vs. 9.75 ± .0.64%, 8.71 ± 0.86 vs. 8.79 ± 0.79%, 9.80 ± 1.16 vs. 9.73 ± 1.06%, p<0.05) despite a significant increase in plasma TG levels (1.11 ± 0.2 vs. 1.91 ± 0.26mmol/L, 1.17 ± 0.15 vs. 1.86 ± 0.28mmol/L, 1.22 ± 0.24 vs. 1.78 ± 0.26mmol/L, p<0.0001 for premenopausal, postmenopausal and hormone replacement groups respectively). The high-fat meal also elicited a significant increase in insulin (9.45 ± 1.34 vs. 39.10 ± 11.32 ± μIU/ml, 8.89 ± 1.17 vs. 32.39 ± 3.17μIU/ml, 7.80 ± 0.81 vs. 32.63 vs. 4.77μIU/ml, p<0.0001). CONCLUSIONS Preserved FMD after a high-fat meal in this study may be explained by the use of healthy active women. Supported by NSERC Canada and the Heart and Stroke Foundation of ON, Canada

Orexins and adipoinsular axis function in the rat

Orexin A and B are recently identified as peptides that are derived from the same precursor and their expression is highly specifically localized in neurons located in the lateral hypothalamic area, a region implicated in the feeding behaviour. These peptides appear to be a part of a complex circuit that integrates the aspects of energy metabolism, cardiovascular function, hormone homeostasis and sleep/wake behaviours. The functional linking of orexins with leptin and insulin suggests the possibility of its involvement in the regulation of the adipoinsular axis, and the present investigation was designed to examine the potential role of orexins in this axis regulation. In all the tested doses (8, 16 and 40 nmol/kg body weight (b.w.)), subcutaneous (s.c.) injections of orexin A caused the significant increase in insulin and leptin blood levels. These elevations were observed 60 and 120 min after peptide administration. On the other hand, after the orexin B administration, elevated insulin and leptin blood concentrations were found only at 60 min of the experiment, and in that time point, the increases were comparable to that evoked by orexin A. In comparison with the control animals, the administration of orexins for 7 days resulted in a significant gain in body weight. Prolonged administration of either orexin A or orexin B significantly elevated insulin and leptin blood concentrations. Under these conditions, the orexin A effect on the leptin secretion was more marked than on the insulin secretion, and this difference is reflected by the lowered insulin/leptin molar ratio. These results suggest that orexins play an important role in the adipoinsular axis function and may be a significant regulator of both insulin and leptin secretion. In this regard, we suggest the updated functional model of Kieffer and Habener [Am. J. Physiol.: Endocrinol. Metab. 27 (2000) E1] that proposed the adipoinsular axis. Our model is extended by the probable humoral links between orexins and leptin and orexins and insulin and points on the dependence of the effects evoked by orexins, leptin and insulin on the blood glucose levels.

Targeted Disruption of the Pituitary Adenylate Cyclase-Activating Polypeptide Gene Results in Early Postnatal Death Associated with Dysfunction of Lipid and Carbohydrate Metabolism

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hormone belonging to the glucagon superfamily of hormones. These hormones are known to play important roles in metabolism and growth. PACAP is a neuropeptide that causes accumulation of cAMP in a number of tissues and affects the secretion of other hormones, vasodilation, neural and immune functions, as well as the cell cycle. To determine whether PACAP is essential for survival and to evaluate its function(s), we have generated mice lacking the PACAP gene via homologous recombination. We found that most PACAP null mice died in the second postnatal week in a wasted state with microvesicular fat accumulation in liver, skeletal muscle, and heart. Gas chromatography-mass spectrometry showed that fatty acid β-oxidation in liver mitochondria of PACAP−/− mice was not blocked based on the distribution of 3-hydroxy-fatty acids (C6–16) in the plasma. Instead, increased metabolic flux through the β-oxidation pathway was suggested by the presence of ketosis. Also, serum triglycerides and cholesterol were significantly higher (2- to 3-fold) in PACAP null mice than littermates. In the fed state, both serum insulin and blood glucose were normal in 5-d-old null mice compared with their littermates. In contrast, fasted PACAP null pups had a significant increase in insulin, but a decrease in blood glucose compared with littermates. Glycogen in the liver was reduced. These results suggest PACAP is a critical hormonal regulator of lipid and carbohydrate metabolism.

Targeted disruption of the pituitary adenylate cyclase-activating polypeptide gene results in early postnatal death associated with dysfunction of lipid and carbohydrate metabolism.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a hormone belonging to the glucagon superfamily of hormones. These hormones are known to play important roles in metabolism and growth. PACAP is a neuropeptide that causes accumulation of cAMP in a number of tissues and affects the secretion of other hormones, vasodilation, neural and immune functions, as well as the cell cycle. To determine whether PACAP is essential for survival and to evaluate its function(s), we have generated mice lacking the PACAP gene via homologous recombination. We found that most PACAP null mice died in the second postnatal week in a wasted state with microvesicular fat accumulation in liver, skeletal muscle, and heart. Gas chromatography-mass spectrometry showed that fatty acid beta-oxidation in liver mitochondria of PACAP(-/-) mice was not blocked based on the distribution of 3-hydroxy-fatty acids (C6-16) in the plasma. Instead, increased metabolic flux through the beta-oxidation pathway was suggested by the presence of ketosis. Also, serum triglycerides and cholesterol were significantly higher (2- to 3-fold) in PACAP null mice than littermates. In the fed state, both serum insulin and blood glucose were normal in 5-d-old null mice compared with their littermates. In contrast, fasted PACAP null pups had a significant increase in insulin, but a decrease in blood glucose compared with littermates. Glycogen in the liver was reduced. These results suggest PACAP is a critical hormonal regulator of lipid and carbohydrate metabolism.

Effect of electrical field stimulation on insulin and glucagon secretion from the pancreas of normal and diabetic rats.

The effect of electrical field stimulation (EFS) on insulin (INS) and glucagon (GLU) secretion from normal and diabetic rat pancreas is poorly understood. In our study, EFS (5-20Hz, 50 V amplitude and 1.0 ms pulse width), when applied alone, resulted in a significant (p<0.05) increase in INS secretion from the pancreas of both normal and diabetic rats. Atropine (10(-5) M) did not inhibit the EFS (5 Hz)-evoked INS secretion in normal pancreas and failed to alter the effect of EFS (10-20 Hz) on INS secretion from the pancreas of both normal and diabetic rats. Propranolol (Prop) inhibited INS secretion to below basal level in the presence of EFS (5 Hz) but not at EFS (10- 20 Hz). Tetrodotoxin (TTX) also significantly (p = 0.002) inhibited INS secretion from normal pancreas in the presence of EFS (5-20 Hz). The decrease in insulin secretion observed when pancreatic tissue fragments were incubated in Prop and TTX in the presence of EFS was reversed by yohimbine (10(-5) M). In contrast, TTX did not significantly modify INS secretion from diabetic pancreas in the presence of EFS. EFS (5-20 Hz) significantly (p<0.05) increased GLU release from normal and diabetic rat pancreas when applied alone. Neither atropine, Prop nor TTX significantly modified GLU release from the pancreas of either normal or diabetic rats. This suggests that GLU secretion may be controlled through a different pathway. The EFS-evoked INS and GLU secretion is probably executed via different mechanisms. These mechanisms include 1) activation of cholinergic nerves by EFS; 2) EFS of alpha- and beta-adrenergic nerves; 3) activation of non-adrenergic non-cholinergic pathway by EFS; 4) EFS-induced depolarization and subsequent action potential in pancreatic endocrine cells and 5) electroporosity caused by EFS-induced membrane permeability. All of these effects may be summative. In conclusion, EFS (5-20 Hz), when applied alone, can evoke significant increases in INS and GLU secretion from the pancreas of both normal and diabetic rats. Insulin secretion is controlled via alpha-2 adrenergic (inhibition) and beta-adrenergic (stimulation) receptors. Glucagon secretion is enhanced by alpha2 adrenergic stimulation.

Food-related sensory stimuli are able to promote pancreatic polypeptide elevation without evident cephalic phase insulin secretion in human obesity.

The data concerning the cephalic phase of insulin secretion (CPIS) in human obesity are controversial. We investigated the effect of a variety of sensory challenges on CPIS in 17 non-diabetic obese patients (four males, 13 females, mean age 41.1 years, mean BMI 38.7). Water, saccharin, and lemon juice were used as oral stimuli, and a complete meal was simply presented as visual and olfactory stimulations. Twelve healthy normal-weight subjects (four men, eight women, mean age 39.9, mean BMI 22.5) also underwent oral stimulation as controls, and the patients who underwent the sight and smell stimulations were also tested for pancreatic polypeptide (PP) changes in order to verify the occurrence of truly cephalic reflex during the test. Insulin levels were measured before and after each stimulation (every min for the first 5 min, and then after 10, 20, and 30 min). None of the stimuli (saccharin, lemon juice or water retained in the mouth for 2 min and were then spat out; the combined and separate sight and smell of a meal for 2 min) led to a significant increase in insulin in the obese patients (except in the case of one woman after oral stimulation). The oral stimuli led to a variable CPIS in one female and three male controls. Despite the absence of CPIS, the five obese patients undergoing all three sensory stimulations related to the meal (combined sight and smell, sight alone and smell alone) showed an early and significant increase in plasma PP concentrations within the first 3 min; this was more pronounced after the combined than after the separate exposure. Although only preliminary, these results underline the variability but substantial lack of CPIS in obese patients, thus suggesting that it can be considered a relatively rare and unrelevant event even in the presence of a true brain-mediated reflex revealed by the rapid and consistent increase in PP found in our experiments.

Effects of intraoperative glucose administration on circulating metabolites and nitrogen balance during prolonged surgery

Study Objectives: To compare the effects of intraoperative administration of 2.5% glucose or Ringer’s solution on metabolism during prolonged surgery. Design: Prospective, randomized study. Setting: Teaching hospital. Patients: 20 ASA physical status I and II adults patients scheduled for thoracic or abdominal surgery lasting at least 3 hours. Interventions: Patients received Ringer’s solution (Group R) or 2.5% glucose solution (Group G) 10 ml · kg −1 · h −1 during surgery and 2 ml · kg. −1 · h −1 during the first two postoperative hours (Ringer’s or glucose), then 40 ml · kg. −1 · day −1 of 5% intravenous (IV) glucose postoperatively. Measurements and Main Results: Plasma glucose, free fatty acids, ketone bodies, lactate, insulin, glucagon, cortisol, and growth hormone concentrations were determined after an overnight fast (T 0), on induction of anesthesia (T 1), at the end of surgery (T 2), 2 hours thereafter (T 3), and on the following morning (T 4). Capillary blood glucose was determined every 30 minutes from T 1 to T 2. Urinary nitrogen and 3-methylhistidine were measured every day for 5 days. There were no differences between groups in demographic data, anesthesia, or surgical procedures. All data were comparable at baseline and on the following morning. In Group R, no patient experienced hypoglycemia, but plasma fatty acids and ketone bodies increased during surgery. In Group G, glycemia rose to very high levels, with a significant increase in insulin during surgery. Other hormones were the same within the two groups. Urinary nitrogen and 3-methylhistidine were similar in both groups. Conclusion: The absence of glucose infusion in prolonged surgery did not cause hypoglycemia, and no increase in protein catabolism was observed.

Metabolic effects of a single administration of growth hormone on lipid and carbohydrate metabolism in normal-weight and obese subjects

The effects on lipid metabolism of a single intramuscular dose of SR 29001 (0.15 U/kg body wt), a biosynthetic human growth hormone (hGH), were explored in a double-blind randomized crossover vs a placebo study of six normal-weight and six obese subjects (Quetelet Index greater than 120%). Circulating hGH concentrations reached means of 35 and 28 ng/mL in the normal-weight and obese subjects, respectively. Free fatty acids increased in both groups (p less than 0.05); increases in beta-hydroxybutyrate and acetoacetate concentrations were more moderate (NS). Plasma glucose increased significantly despite a significant increase in insulin (p less than 0.002). The lipolytic effect persisted after a standardized 950-kcal meal eaten 5 h after hGH administration. A delayed increase in somatomedin-C and decreases in blood urea and total cholesterol were also observed (p less than 0.05). Despite increased insulin secretion, biosynthetic hGH produced a significant increase of lipolysis in both groups, which was only partially suppressed by food.

Response of Plasma Glucose, Fructose and Insulin to Dietary Glucose and Fructose in the Lactating Sow

Twenty-two Hampshire-Yorkshire X Large White sows of second and third parity were allotted randomly to one of three dietary treatments. Five sows were fed 6.0 kg/day of a corn-soybean meal lactation diet (control diet). Twelve sows were fed the control diet in which 24% of the composition was supplied by corn syrup containing 72% fructose on a dry matter basis (fructose diet) and five sows were fed the control diet in which 24% of the composition was supplied by powdered dextrose (glucose diet). All diets were fed from days 1 through 21 of lactation. Blood was collected from all sows immediately prior to feeding and hourly for 6 hours postprandial via jugular vein cannulae following a single feeding on seven separate but nonconsecutive days during the 21-day period. Fructose was absorbed from the digestive tract of sows as evidenced by elevated (P < 0.01) concentrations of fructose in plasma. Sows fed the fructose diet also had higher (P < 0.01) plasma glucose concentrations than did those fed the glucose and control diets. The concomitant elevated glucose concentration following ingestion of the fructose diet was not associated (P > 0.10) with increased insulin concentration. Fructose in plasma was associated with a slight but significant increase in insulin although the mean concentration of insulin in plasma was only one-third that measured in sows fed the glucose and control diets. These data suggest that fructose in vivo has a glucose-sparing effect presumably mediated through a physiological mechanism that lowers insulin concentration.

Insulin response to secretogogues in sheep exposed to cold.

1. The effects of cold exposure on insulin secretion in response to intravenous injections of glucose, butyrate, arginine, glucagon and tolbutamide were examined in ten sheep exposed to a temperature of 0 degree C for 4-13 days. 2. Cold exposure produced a marked decrease in insulin responses to glucose and butyrate to a level similar to that caused by arginine administration. Cold exposure brought about a significant but only slight decrease in the insulin response to arginine. 3. Glucagon injection resulted in a markedly lower secretion of insulin in the cold than in the warm environment. 4. In the warm environment tolbutamide caused a significant increase in insulin secretion, but in the cold environment did not produce any statistically significant increase in plasma insulin. 5. It is concluded that cold exposure decreases insulin secretion in response to a variety of stimuli.

The metabolic response to yellow fever immunization: protein-sparing modified fast

The metabolic response to yellow fever immunization was investigated in five obese patients who were consuming a protein-sparing modified fast for 3 wk. Fasting 1/2, 1, and 2 h postprandial values for insulin, glucagon, glucose, lactate, beta hydroxybutyrate, acetoacetate, and free fatty acids were assessed before and the 1st, 3rd, and 5th day after immunization. The hormone and substrate responses to meat ingestion in patients well adapted to a protein-sparing modified fast and prior to infection was a rise in glucagon, no change in insulin, lactate, or ketone bodies and slight increase in serum free fatty acid and glucose levels. Over the entire period a significant (p less than 0.01) postprandial rise in glucagon was noted. Significant increases in insulin (p less than 0.01) and lactate (p less than 0.01) and falls in beta hydroxybutyrate (p less than 0.01) and acetoacetate (p less than 0.01) were noted in the postinfection period. There was also a significant interaction of diet and infection to increase insulin levels (p less than 0.05). The clinically mild infection produced by yellow fever immunization elicits a metabolic response which thus may be useful to investigate intermediary metabolism in the hospital setting.