Oral Meal Research Articles

Acute Metabolic Effects of Exenatide in Patients With Type 1 Diabetes With and Without Residual Insulin to Oral and Intravenous Glucose Challenges

OBJECTIVEGlucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the gastrointestinal tract. Treatment with GLP-1 analogs has proven to be of clinical use for patients with type 2 diabetes. Patients with type 1 diabetes, particularly those with residual β-cell function, may also respond to treatment, but the acute metabolic effects of GLP-1 analogs on these patients in reaction to both oral and intravenous glucose challenges are not well understood.RESEARCH DESIGN AND METHODSSeventeen patients with type 1 diabetes, half of whom had residual insulin production, underwent two mixed-meal tolerance tests (MMTTs) and two intravenous glucose tolerance tests (IVGTTs), with and without pretreatment with exenatide. No exogenous bolus insulin was administered for the studies. Glucose excursions, insulin secretion rates (ISRs), and levels of glucagon, endogenous GLP-1, and gastric inhibitory polypeptide were measured after the meal or glucose loads.RESULTSDuring the MMTT, glucose levels were suppressed with exenatide in patients with or without residual insulin production (P = 0.0003). Exenatide treatment did not change the absolute ISR, but the ISR to glucose levels were increased (P = 0.0078). Gastric emptying was delayed (P = 0.0017), and glucagon was suppressed (P = 0.0015). None of these hormonal or glucose changes were detected during the IVGTT with exenatide administration.CONCLUSIONSExenatide showed a significant antidiabetogenic effect prior to an oral meal in patients with type 1 diabetes involving glucagon suppression and gastric emptying, while preserving increased insulin secretion. GLP-1 analogs may be useful as an adjunctive treatment in type 1 diabetes.

Effect of the glucagon-like peptide-1 receptor agonist lixisenatide on postprandial hepatic glucose metabolism in the conscious dog

The impact of the GLP-1 receptor agonist lixisenatide on postprandial glucose disposition was examined in conscious dogs to identify mechanisms for its improvement of meal tolerance in humans and examine the tissue disposition of meal-derived carbohydrate. Catheterization for measurement of hepatic balance occurred ≈16 days before study. After being fasted overnight, dogs received a subcutaneous injection of 1.5 μg/kg lixisenatide or vehicle (saline, control; n = 6/group). Thirty minutes later, they received an oral meal feeding (93.4 kJ; 19% protein, 71% glucose polymers, and 10% lipid). Acetaminophen was included in the meal in four control and five lixisenatide dogs for assessment of gastric emptying. Observations continued for 510 min; absorption was incomplete in lixisenatide at that point. The plasma acetaminophen area under the curve (AUC) in lixisenatide was 65% of that in control (P < 0.05). Absorption of the meal began within 15 min in control but was delayed until ≈30-45 min in lixisenatide. Lixisenatide reduced (P < 0.05) the postprandial arterial glucose AUC ≈54% and insulin AUC ≈44%. Net hepatic glucose uptake did not differ significantly between groups. Nonhepatic glucose uptake tended to be reduced by lixisenatide (6,151 ± 4,321 and 10,541 ± 1,854 μmol·kg(-1)·510 min(-1) in lixisenatide and control, respectively; P = 0.09), but adjusted (for glucose and insulin concentrations) values did not differ (18.9 ± 3.8 and 19.6 ± 7.9 l·kg(-1)·pmol(-1)·l(-1), lixisenatide and control, respectively; P = 0.94). Thus, lixisenatide delays gastric emptying, allowing more efficient disposal of the carbohydrate in the feeding without increasing liver glucose disposal. Lixisenatide could prove to be a valuable adjunct in treatment of postprandial hyperglycemia in impaired glucose tolerance or type 2 diabetes.

GLP-1 Response to a Mixed Meal: What Happens 10 Years after Roux-en-Y Gastric Bypass (RYGB)?

Oral meal consumption increases glucagon-like peptide 1 (GLP-1) release which maintains euglycemia by increasing insulin secretion. This effect is exaggerated during short-term follow-up of Roux-en-y gastric bypass (RYGB). We examined the durability of this effect in patient with type 2 diabetes (T2DM) >10 years after RYGB. GLP-1 response to a mixed meal in the 10-year post-RYGB group (n = 5) was compared to lean (n = 9), obese (n = 6), and type 2 diabetic (n = 10) controls using a cross-sectional study design. Analysis of variance (ANOVA) was used to evaluate GLP-1 response to mixed meal consumption from 0 to 300 min, 0-20 min, 20-60 min, and 60-300 min, respectively. Weight, insulin resistance, and T2DM were also assessed. GLP-1 response 0-300 min in the 10-year post-RYGB showed a statistically significant overall difference (p = 0.01) compared to controls. Furthermore, GLP-1 response 0-20 min in the 10-year post-RYGB group showed a very rapid statistically significant rise (p = 0.035) to a peak of 40 pM. GLP-1 response between 20 and 60 min showed a rapid statistically significant (p = 0.041) decline in GLP-1 response from ~40 pM to 10 pM. GLP-1 response in the 10-year post-RYGB group from 60 to 300 min showed no statistically significant difference from controls. BMI, HOMA, and fasting serum glucose before and >10 years after RYGB changed from 59.9 → 40.4, 8.7 → 0.88, and 155.2 → 87.6 mg/dl, respectively, and were statistically significant (p < 0.05). An exaggerated GLP-1 response was noted 10 years after RYGB, strongly suggesting a durability of this effect. This phenomenon may play a key role in maintaining type 2 diabetes remission and weight loss after RYGB.

Comparing glycaemic and insulinaemic responses of ponies and horses to dietary glucose

s / Journal of Equine Veterinary Science 31 (2011) 230-356 301 Comparing glycaemic and insulinaemic responses of ponies and horses to dietary glucose K.D. Tinworth , S.L. Raidal , P.A. Harris , M.N. Sillence , and G.K. Noble 1 1 Charles Sturt University, Wagga Wagga, NSW 2650, Australia, WALTHAM Centre for Pet Nutrition, Waltham-on-the-Wolds, Leicestershire, UK, Queensland University of Technology, Brisbane, Qld 4001, Australia Introduction: It is known that horses are typically more insulin sensitive than ponies [1], and correlations have been shown between morphometry and insulin sensitivity [2]. The aim of this study was to quantify the glucose and insulin responses to the same meal in horses with moderate body condition scores (BCS) as well as obese ponies, thereby using both disparate breeds and morphometry. Materials and Methods: Eight mature pony mares (Shetlandand Welsh-cross, non-Cushingoid, no known history of laminitis) with a (mean SD) BW 201.4 48.8 kg, 10 3.3 yrs and BCS range 7 to 9 [3], presumed to be insulin-resistant (I-R) based on morphometry, with cresty neck scores (CNS) 3/5 [4], were compared with 12 mature light-breed mares, presumed nonI-R, with a BW 473 61.6 kg, 4.7 1.9 yrs, BCS range 3 to 5/9 and CNS 1/5. They were kept in groups in grass paddocks (non-structural carbohydrates (NSC) 10.5% dry matter (DM)) for 21 days prior to the study. They were stabled and given hay the night before the Oral Meal Tolerance Test (OMTT) when they were fed either hay + rice bran (Cool Conditioner, CopRice, Leeton, NSW Australia; H Meal: 1% BW oaten hay + 200 g rice bran, Pony NSC 621 127 g DM, Horse NSC 1214 151 g DM) or hay + rice bran + glucose (H+G Meal: 1% BW oaten hay + 0.75 g/kg BW glucose, Pony NSC 2319 478 g DM, Horse NSC 4549 569 g DM). Four ponies and six horses were fed the H Meal, and the other four ponies and six horses received the H+G Meal around 0900 h. All animals had consumed their rice bran glucose within 2 min and their hay within 60 min. The glucose (G) and insulin (I) responses to the meals were measured in blood samples taken every 15 min from the time of feeding (t1⁄40) for 180 min. G and I responses were analysed with repeated measures analysis over time, with 2 treatments, meal type and presumed I-R-status. An autoregressive first order model was used for correlation through time for individual animals. G and I values were Log10transformed to normalize the data. Significance was taken as being P < .05. Results and Discussion: The G and I responses to the two meals are shown in Figure 1. All comparisons showed highly significant effects of time and meal type, with interactions between time, meal type and presumed I-R-status (P < .001). H Meal Peak G concentrations [G] were similar (6.28 0.52 vs 5.48 0.36 mmol/L for horses vs ponies respectively) but the peak I concentrations [I] were higher (P < .001) in the ponies (36.67 20.4 vs 8.61 3.91 mU/mL). Horses maintained higher circulating [G], in keeping with their lower insulin response. In contrast, the ponies secreted proportionally more insulin than the horses and maintained their [G] at a lower level. H+G Meal Peak [G] for the horses was 9.05 .98 mmol/L. It is unclear whether the ponies had reached a peak [G] by 180 min but the maximum [G] recorded was 7.65 1.34 mmol. Peak [I] for the horses was higher (P < .001) than following the H Meal (25.4 8.16 mU/mL). However, the peak [I] for the ponies was markedly higher than for the horses (H or H+G) or ponies with the H meal, at 403 362.79 mU/mL by 120 min, and was still significantly elevated at 180 min. In response to the H+G Meal, the horses again attained higher circulating [G] than the ponies, but with significantly lower [I] effectively disposed of the glucose to return it to near-basal concentrations by 180min. In contrast, overall, the ponies, despite their enhanced insulinaemia, did not control the hyperglycaemia seen within the time period monitored. Conclusion: This study illustrated the magnitude of difference in G and I responses of horses and ponies to the same meals. We showed clearly how poorly ponies control their meal-derived glycaemia when challenged with free glucose. The prediction of insulin sensitivity using morphometry and breed was borne out by the G and I responses to a meal. It also showed how free glucose ingestion can cause a sustained hyperinsulinaemia in ponies. These results provide a possible insight into why obese ponies appear to be more at risk of laminitis [5] when exposed to grass high in simple sugars, than horses.

Glucose lowering effect of transgenic human insulin-like growth factor-I from rice: in vitro and in vivostudies

BackgroundHuman insulin-like growth factor-I (hIGF-I) is a growth factor which is highly resemble to insulin. It is essential for cell proliferation and has been proposed for treatment of various endocrine-associated diseases including growth hormone insensitivity syndrome and diabetes mellitus. In the present study, an efficient plant expression system was developed to produce biologically active recombinant hIGF-I (rhIGF-I) in transgenic rice grains.ResultsThe plant-codon-optimized hIGF-I was introduced into rice via Agrobacterium-mediated transformation. To enhance the stability and yield of rhIGF-I, the endoplasmic reticulum-retention signal and glutelin signal peptide were used to deliver rhIGF-I to endoplasmic reticulum for stable accumulation. We found that only glutelin signal peptide could lead to successful expression of hIGF-I and one gram of hIGF-I rice grain possessed the maximum activity level equivalent to 3.2 micro molar of commercial rhIGF-I. In vitro functional analysis showed that the rice-derived rhIGF-I was effective in inducing membrane ruffling and glucose uptake on rat skeletal muscle cells. Oral meal test with rice-containing rhIGF-I acutely reduced blood glucose levels in streptozotocin-induced and Zucker diabetic rats, whereas it had no effect in normal rats.ConclusionOur findings provided an alternative expression system to produce large quantities of biologically active rhIGF-I. The provision of large quantity of recombinant proteins will promote further research on the therapeutic potential of rhIGF-I.

Endogenous GLP-1 Regulates Postprandial Glycemia in Humans: Relative Contributions of Insulin, Glucagon, and Gastric Emptying

Synthetic glucagon-like peptide-1 (7-36)amide (GLP-1) lowers postprandial (pp) glycemia by stimulating insulin and inhibiting glucagon release and delaying gastric emptying (GE). However, the biological effects of the endogenous peptide and their relative contributions to pp glycemia remain to be defined in detail. Using the specific GLP-1 receptor antagonist exendin(9-39)amide [Ex(9-39)], we studied the exact impact of GLP-1 after an oral meal in humans. After a 50-min basal period, 12 healthy subjects ingested a 412-kcal mixed semisolid meal containing 30 g oatmeal, labeled with 99mTc-Sn-colloid. GE was measured by high-resolution scintigraphy until 210 min after meal ingestion. In random order, saline or Ex(9-39) at 900 pmol/kg·min was infused iv. Additionally, in six subjects gastric motility was measured by antroduodenal manometry and a gastric barostat in parallel. Ex(9-39) increased pp blood glucose excursions during the first 60 min after the meal (43.9 ± 5.4 vs. 35.9 ± 3.6 mg/dl, P = 0.008; pp peak glucose 154.0 ± 5.5 vs.141.0 ± 4.7 mg/dl, P = 0.009). Insulin increased slightly with Ex(9-39), whereas the insulin to glucose ratio was unchanged. pp glucagon was significantly increased with Ex(9-39) (7.5 ± 2.4 vs. 3.2 ± 2.1 pg/ml, P = 0.024). GE and accordingly gastric motility did not change with Ex(9-39). Multiple linear regression analysis revealed only changes of pp glucagon to be significantly associated with increased pp glycemia under Ex(9-39) (R = 0.678, P = 0.015). Released after an oral meal, GLP-1 lowers pp glycemia. In this study, the inhibition of glucagon release was a major determinant of the acute GLP-1 action in healthy subjects. In contrast, gastric emptying was not changed by GLP-1 receptor antagonism.

認知症症例の退院援助に関する検討

The goal of this study was to clarify how the post-discharge support by a full time psychiatric social worker (PSW) in a dementia ward affected the discharge status of dementia patients. Patients who were discharged from a dementia ward were examined for hospitalization, post-discharge status, nutrition methods, treatment drugs, and relationship with discharge support performed by the PSW. A total of 192 cases met the requirements for this examination, and approximately half (94, 49.0%) of these patients had Alzheimer disease. Fifty-two patients (32.3%) moved to home care. Forty-five patients visited our hospital for treatment, while 17 visited other medical institutions for treatment. Thirty-four patients (17.7%) moved to other medical institutions, and the remaining 96 patients (50.0%) entered other institutions. About half of these patients entered insurance care facilities for the elderly, and the number of entered cases decreased in the order of special elderly nursing homes, paid homes for the elderly, and group homes. The highest mean support frequency per case was more than 50 occasions and 800 minutes for a paid home for the elderly. This support decreased in the order of special elderly nursing homes, insurance care facilities, and group homes. Cases treated at other medical institutions had the shortest hospitalization, but these cases had a greater mean support frequency than the cases treated at our hospital. The lowest mean support frequency was for oral meal intake while the highest mean support frequency was for nourishment by gastrostomy, with a significant difference between both (P<0.01). Only for cases that entered insurance care facilities for the elderly was there significantly more support frequency for cases that took donepezil hydrochloride than cases that took other drugs (P<0.03). After discharge from a dementia ward, the PSW spent a significant amount of time on discharge support, and this discharge support was indispensable. Hospitalization at a medical institution or admission to facilities was associated with a higher degree of discharge support than home care. Furthermore, patients who were hospitalized at a long-term medical treatment institution, or those who entered an insurance care facility for the elderly, needed frequent support for drug administration.

Changes in superior mesenteric artery blood flow after oral, enteral, and parenteral feeding in humans*

Alterations in splanchnic blood flow cause gut ischemia and may predispose to gut-derived sepsis. Increases in superior mesenteric artery (SMA) blood flow occur follow the oral ingestion of food, but the effects of enteral nutrition (EN) on splanchnic perfusion are poorly defined and those of parenteral nutrition (PN) are unknown in humans. The aim of this study was to investigate changes in SMA flow in healthy controls and patients receiving adjuvant nutrition. Qualitative before-after study. Intensive care and general wards at Scarborough Hospital, Scarborough, United Kingdom. Fourteen healthy volunteers and 20 consecutive hemodynamically stable patients receiving adjuvant nutrition. Oral, EN, or PN after an overnight fast. Duplex ultrasonography was used to assess SMA flow after an overnight fast. Subjects were then rescanned 3 hrs later after commencement of the appropriate test feed so that postprandial flows could be determined. Of the 20 patients recruited, 10 were receiving EN (120 kcal) and 10 PN (175 kcal). Of the 14 volunteers, three received no feed before their second scan (controls), six received an oral meal (530 kcal), and five received EN (120 kcal). Changes in SMA flow within groups were assessed. The control (fasting) volunteers showed no change between the two scans (p = 1.000). All subjects fed intraluminally demonstrated significant increases in postprandial SMA blood flow. Conversely, all patients fed parenterally showed decreased postprandial SMA flows with a median (interquartile range) fasting SMA flow of 14.5 (4.8-24.8) mL/sec, which decreased to 6.1 (2.4-9.2) mL/sec postprandially (p = 0.013). Splanchnic flow is modulated by the route of feeding. The clinical significance of these findings requires further investigation as they may be important in the management of the critically ill patient, particularly in those with cardiovascular instability or any patient predisposed to gut ischemia.

Chronic administration of alogliptin, a novel, potent, and highly selective dipeptidyl peptidase-4 inhibitor, improves glycemic control and beta-cell function in obese diabetic ob/ob mice

Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes by increasing plasma active glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide levels. However, the effects of chronic DPP-4 inhibition on in vivo beta-cell function are poorly characterized. We thus evaluated the chronic effects of the DPP-4 inhibitor alogliptin benzoate (formerly SYR-322) on metabolic control and beta-cell function in obese diabetic ob/ob mice. Alogliptin (0.002%, 0.01%, or 0.03%) was administered in the diet to ob/ob mice for 2 days to determine effects on plasma DPP-4 activity and active GLP-1 levels and for 4 weeks to determine chronic effects on metabolic control and beta-cell function. After 2 days, alogliptin dose-dependently inhibited DPP-4 activity by 28–82% and increased active GLP-1 by 3.2–6.4-fold. After 4 weeks, alogliptin dose-dependently decreased glycosylated hemoglobin by 0.4–0.9%, plasma glucose by 7–28% and plasma triglycerides by 24–51%, increased plasma insulin by 1.5–2.0-fold, and decreased plasma glucagon by 23–26%, with neutral effects on body weight and food consumption. In addition, after drug washout, alogliptin (0.03% dose) increased early-phase insulin secretion by 2.4-fold and improved oral meal tolerance (25% decrease in glucose area under the concentration–time curve), despite the lack of measurable plasma DPP-4 inhibition. Importantly, alogliptin also increased pancreatic insulin content up to 2.5-fold, and induced intense insulin staining of islets, suggestive of improved beta-cell function. In conclusion, chronic treatment with alogliptin improved glycemic control, decreased triglycerides, and improved beta-cell function in ob/ob mice, and may exhibit similar effects in patients with type 2 diabetes.

Minimally Invasive Surgery for Achalasia: Combined Experience of Two European Centers

The present report summarizes 12 cases with achalasia treated with laparoscopic Heller myotomy and anterior fundoplication according to the method of Thal and Dor. From 1997 to 2005 at 2 institutions in Europe, 12 patients (7 male and 5 female, ages ranging from 3.5 to 7 years) were treated for esophageal achalasia (EA) with laparoscopic Heller myotomy and anterior fundoplication according to Thal and Dor. In 1 case a perforation of the esophageal mucosa occurred, which was promptly treated during surgery. Follow-up ranged from 18 to 60 months and included clinical examination and barium radiography of the upper digestive tract. Postoperatively, 10 patients showed a normal weight curve and complete resolution of symptoms. All patients showed complete regression of digestive and respiratory symptoms from the first examination, with a normal oral meal intake and an improvement of weight and height parameters. One case required repeat intervention after 2 years because of persisting pain; in this case surgery revealed an insufficient myotomy. Modified extramucosal Heller cardiomyotomy associated with 180 degree anterior antireflux plastic surgery (according to Thal and Dor's procedures) is a useful and safe procedure in the treatment of EA in pediatric patients. Our data, which are supported by long-term follow-up, also stress the relevance of anterior fundoplication in preventing postoperative gastroesophageal reflux.

Appearance of Individual Amino Acid Concentrations in Arterial Blood During Steady‐State Infusions of Different Amino Acid Formulations to ICU Patients in Support of Whole‐Body Protein Metabolism

Previous work has demonstrated a relationship between arterial amino acid concentrations and uptake of amino acids across peripheral tissues in healthy volunteers, as well as in chronically and acutely ill patients. The aim of the present study was to evaluate whether different amino acid profiles in commercially available amino acid formulations are translated into significantly different arterial amino acid concentrations presumably high enough to promote protein metabolism in intensive care unit (ICU) patients. Nonprotein calories (60% glucose: 40% lipid) were simultaneously and constantly infused over 72 hours. Different free amino acid solutions were infused at random to each patient for 24 hours in order to determine the appearance of steady-state arterial concentrations of individual amino acids. Basal metabolic and nutrition states were defined after a 12-hour infusion period with glucose in each patient. Healthy volunteers receiving a standardized oral meal served as reference subjects in measurements of venous amino acid concentrations after normal oral food intake. The sum of all amino acids in arterial plasma increased significantly during steady-state infusions of all the free amino acid solutions vs basal state in ICU patients. Only glutamine, taurine, and tyrosine did not increase at all vs basal state during steady-state infusions of the 3 formulations. Alanine, arginine, citrulline, glycine, histidine, serine, methionine, phenylalanine, valine, and ornithine showed different concentration among the amino acid solutions during infusions. Healthy volunteers had significantly higher overall concentrations of amino acids in both fasted and fed state compared with ICU patients, which indicates that free amino acid solutions remain a limiting component in artificial nutrition to patients to promote arterial amino acid concentrations in the artificially fed state. It appears important to continue further improvement of composition profile in solutions of free amino acids to promote adequate uptake across organ beds in promotion of protein balance in artificially nourished patients.

Metabolic response to oral meal tolerance test in nondiabetic subjects with non-alcoholic steatohepatitis (NASH): Naga Chalasani, Mark Deeg, David W Crabb, Indiana University School of Medicine, Indianapolis, IN

Metabolic response to oral meal tolerance test in nondiabetic subjects with non-alcoholic steatohepatitis (NASH): Naga Chalasani, Mark Deeg, David W Crabb, Indiana University School of Medicine, Indianapolis, IN

Differentially expressed midgut transcripts in Culicoides sonorensis (Diptera: ceratopogonidae) following Orbivirus (reoviridae) oral feeding.

Understanding the vector insect's gene expression response to a virus infection may aid design of control measures for arbovirus diseases. Culicoides sonorensis is a vector of several agriculturally important pathogens, such as epizootic haemorrhagic disease virus (EHDV) that causes disease in ruminants. Two approaches, differential display and suppression subtractive hybridization, were used to identify 400+ Culicoides transcripts that were more abundant in midguts 1 day following an oral meal containing EHDV. Of these, quantitative PCR confirmed seven to be more abundant in virus-fed midguts than controls. One such transcript encodes a putative RNA editase, CsRED1, induced by dsRNA. Transcripts encoding putative receptors involved in cell differentiation included CsLAR, a protein tyrosine phosphatase, and CsFZ2, homologous to the wingless receptor in D. melanogaster. Transcripts encoding putative translation machinery components included CseIF3, CseIF5A and CsRPS6. Overall, the cDNA fragments identified in this study increased in the midgut at one day postfeeding; by 2 days postfeeding, increases in transcript levels shifted from the midgut to the remainder of the infected midge.

Regulation of gastric function by endogenous gastrin releasing peptide in humans: studies with a specific gastrin releasing peptide receptor antagonist

BACKGROUND AND AIMSThe main goal of our study was to characterise the activity of BIM26226 as a peripheral gastrin releasing peptide (GRP) receptor antagonist in healthy human subjects and to...

A mutual inhibitory effect on absorption of sphingomyelin and cholesterol

Several studies have shown that there is a strong physical interaction between cholesterol and sphingomyelin (SM). The critical factor is thought to be the high degree of saturation in the very long acyl chains of SM. In this study we examined the effects of SM on cholesterol absorption in the rat and compared them with those of phosphatidylcholine (PC). Cholesterol absorption was studied by use of the dual-isotope plasma ratio method. We also studied the effect of sterols on the fecal excretion of undigested SM and its metabolites after a single oral meal of 3H-dihydrosphingosine-labeled SM. When cholesterol was given dissolved in soybean oil, without addition of SM or other phospholipids, absorption was 68 ± 12% in the rat intestine. As a general feature the absorption was less efficient from the cholesterol/phospholipid dispersions. In dispersions with cholesterol and SM, the lowest cholesterol absorption (9 ± 2%) was seen with a cholesterol:SM molar ratio of 1:1. With dispersions of cholesterol and different PC substrates the absorption of cholesterol was lower with saturated PC (16 ± 8%) than with soybean-PC (22 ± 4%) or dioleoyl PC (23 ± 8%). Uptake of SM in the rat intestine was reduced by sterols. For example, percentage recovery of 3H radioactivity in fecal lipids was 38 ± 8% when SM was given with cholesterol and 16 ± 3% without any sterol. One third of the radioactivity in feces was present as ceramide. Sitostanol had the same effect on uptake of SM as cholesterol. This study shows that when rats are fed mixtures of SM and cholesterol the intestinal uptake of both lipids is decreased. By feeding mixtures of SM and sterols the exposure of the colon to ceramide can be increased.

Obese mice have higher insulin receptor levels in the hepatocyte cell nucleus following insulin stimulation in vivo with an oral glucose meal

Internalization of the insulin receptor occurs following insulin binding at the cell surface, which serves to attenuate the insulin signal as well as modulate the number of surface insulin receptors. Obese animals exhibit decreased cell surface insulin receptor number as well as defects in insulin receptor internalization and processing. The insulin receptor may also translocates to the nucleus of hepatocytes and adipocytes following stimulation of cells with insulin. The objective of this study was to determine if insulin receptor trafficking to the hepatocyte cell nucleus could be observed in vivo and whether this process was altered in obese compared to lean mice. Mice were fasted for 12 h to reduce serum insulin to basal levels. Animals were then given an oral meal of glucose to stimulate the binding of insulin to receptor in vivo. Hepatocyte plasma membrane and nuclei were fractionated to purity following the glucose meal. Levels of insulin receptor were determined using insulin binding assays and a Western blotting assay using anti-insulin receptor antibody. As the amount of serum insulin increased following the glucose meal, a corresponding increase in nuclear insulin binding occurred in lean animals but not obese animals ( P<0.05). Following the glucose meal, insulin receptor detected in the cell nucleus was increased in obese compared to lean mice ( P<0.05). Thus insulin receptor translocation to the nucleus was demonstrated in vivo following a glucose meal in hepatocytes of both lean and obese animals. It is suggested that serum hyperglycemia and hyperinsulinemia in obese mice increased translocation of the insulin receptor to the nucleus.

Blood glucose clearance after feeding and exercise in polysaccharide storage myopathy

Polysaccharide storage myopathy (PSSM) in Quarter Horses (QH) and QH crosses is a glycogen storage disorder in which blood glucose clearance and insulin sensitivity, following an i.v. or oral glucose challenge, are enhanced. Exercise is known also to enhance glucose uptake into skeletal muscle in many animal species. Therefore, the purpose of this study was to compare the effect of exercise on glucose clearance in PSSM and control horses when an oral carbohydrate meal (8 Mcal sweet feed) was fed following either 12 h fasting alone (NEX protocol) or following fasting and a standard exercise protocol (EX protocol). In the NEX protocol, horses fasted 12 h and then were fed 8 megacalories (Mcal) of sweet feed (2.3 kg). In the EX protocol, horses were fed sweet feed 2 h after an exercise test (SET). Blood glucose was analysed for < 480 min after feeding. Muscle biopsies were taken before and after the EX protocol. With the NEX protocol, the mean of all blood glucose and insulin concentrations were significantly lower in fed-PSSM horses than controls (P < 0.013). The EX protocol in control horses caused a less pronounced percentage change in glucose concentration from baseline following feeding compared to the NEX protocol (mean peak EX 26.5% vs. NEX 70.2%, respectively) (P < 0.0003). In PSSM horses, the EX protocol also resulted in a lower percent change in glucose concentration following feeding compared to the NEX protocol (44.7 vs. 67.5%, respectively) (P = 0.021). The magnitude of the difference in percentage change of blood glucose concentration with the EX protocol was less in PSSM than that seen for controls (mean peak PSSM-EX 44.7% vs. 26.5% for controls, respectively) (P < 0.006). No significant differences in the insulin:glucose ratios were found for control horses between NEX and EX. In PSSM horses, the insulin:glucose ratio was significantly increased in the EX vs. NEX. In conclusion, exercise in normal horses results in enhanced glucose clearance following feeding without altering insulin:glucose ratios. At rest, PSSM horses have lower insulin:glucose ratios after feeding than normal horses, however, exercise in PSSM horses significantly increases insulin:glucose ratios. This may explain the beneficial effect of daily exercise for preventing rhabdomyolysis in horses with PSSM.

Glycemic Index and Insulin Response to a Liquid Nutritional Formula Compared with a Standard Meal

Objective: To determine the glycemic index and metabolic responses to a nutritional formula, and to compare these responses to those following an oral glucose meal and a standard test meal.Methods: Six male and six female healthy non-diabetic volunteers aged 18 to 48 years met screening examination and laboratory assessment criteria. Three test meals were administered, each containing 50 g of carbohydrate: nutritional formula (NF), standard test meal (ST) and a glucose test meal (GT). Each subject underwent the three test meals on separate days in randomized sequence. Blood samples were taken at intervals over 5 hours for determination of glucose, insulin and triglycerides.Results: The glycemic index was similar for the NF (60.8±13.1) and for the ST (57.8±12.9) meals. The incremental area under the curve for glucose was similar for NF and ST, but each was significantly lower than for the GT meal. The total area under the curve for insulin was significantly greater for the NF meal than for the ST meal. The serum triglyceride responses were similar for NF and ST meals.Conclusion: In healthy non-diabetic subjects, the blood glucose and triglyceride responses are similar for a nutritional formula compared to an isoenergetic standard test meal. However, the insulin response differs. This information is important in managing tube-fed patients.

Does Helicobacter pylori-induced gastritis enhance food-stimulated insulin release?

The fact that H. pylori gastritis results in an increased secretion of basal and meal-stimulated gastrin, which is also a physiologic amplifier of insulin release directed us to investigate whether H. pylori gastritis may lead to an enhancement of nutrient-stimulated insulin secretion. For this purpose, we have investigated the insulin responses to both oral glucose and a mixed meal in 15 patients with H. pylori gastritis before and one month after the eradication therapy and also in 15 H. pylori-negative control subjects. The areas under the curve (AUC) for serum insulin following both oral glucose and a mixed meal in the patients with H. pylori gastritis before the eradication were significantly (P < 0.05) higher than those in the H. pylori-negative controls. After the eradication of H. pylori, the AUC for serum insulin following oral glucose and mixed meal decreased by 9.4% and 13.1%, respectively (P < 0.001 in both), and serum basal and meal-stimulated gastrin levels decreased significantly (P < 0.001). These results suggest that H. pylori gastritis enhances glucose and meal-stimulated insulin release probably by increasing gastrin secretion.

Portal Vein Insulin Flux and Arterial Glucose Fluctuations in Response to an Oral Meal Test in Islet Cell-Transplanted Dogs

Insulin flux was determined in the portal vein and simultaneously arterial blood glucose was measured before and during an oral glucose meal in conscious normal and pancreatic islet cell-autotransplanted dogs to test their insulinogenic reserve. These dogs had previously been chronically instrumented with blood flow probes on the portal vein and carotid artery, and blood sampling catheters in the portal vein, hepatic vein, carotid artery, and right external jugular vein. Such a model permits quantitative portal-peripheral comparisons and assessment of hepatic extraction. Sixteen dogs, 10 normal (N) and six long-term (2 months to 2 yrs) islet cell-transplanted dogs (IT) were fed an oral glucose meal as a test (OMT). Baseline portal vein insulin fluxes (PVF) were similar in both groups (25.6 +/- 0.04 pmol/min in N and 24.7 +/- 19.4 pmol/min in IT). Immediately after OMT, PVF rose to 248.2 +/- 40.9 pmol/min in N, but only to 55.9 +/- 17.9 pmol/min in IT. After 30 min PVF peaked for the second time in N at 156 +/- 35.9 pmol/min, declining slowly to baseline after 3 h. In IT, a similar peak at 30 min was seen (143.7 +/- 22.1 pmol/min), declining to a value not different from baseline after 3 h. However, cumulative insulin PV fluxes in the two groups over 3 h were not different. Differences were also seen in postprandial glucose fluctuations, which reached a maximum excursion of 11.8 +/- 0.45 mM in IT, while never rising above 7.8 +/- 0.33 mM in N. After 3 h both groups had similar glucose values.(ABSTRACT TRUNCATED AT 250 WORDS)