Effect of stress hormones on splanchnic substrate and insulin disposal after glucose ingestion in healthy humans

We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load, we here compare hypothalamic BOLD signal changes subsequent to an oral vs. an intravenous (iv) glucose challenge in healthy humans. Seven healthy, normal-weight men received four interventions in random order after an overnight fast: 1) ingestion of glucose solution (75 g in 300 ml) or 2) water (300 ml), and 3) iv infusion of 40% glucose solution (0.5 g/kg body wt, maximum 35 g) or 4) infusion of saline (0.9% NaCl, equal volume). The BOLD signal was recorded as of 8 min prior to intervention (baseline) until 30 min after. Glucose infusion was associated with a modest and transient signal decline in the hypothalamus. In contrast, glucose ingestion was followed by a profound and persistent signal decrease despite the fact that plasma glucose levels were almost threefold lower than in response to iv administration. Accordingly, glucose ingestion tended to suppress hunger more than iv infusion ( P < 0.1). We infer that neural and endocrine signals emanating from the gastrointestinal tract are critical for the hypothalamic response to nutrient ingestion.

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Free fatty acid-induced peripheral insulin resistance augments splanchnic glucose uptake in healthy humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00329.2001 ◽

2002 ◽

Vol 283 (2) ◽

pp. E346-E352 ◽

Cited By ~ 14

Author(s):

Mandeep Bajaj ◽

Rachele Berria ◽

Thongchai Pratipanawatr ◽

Sangeeta Kashyap ◽

Wilailak Pratipanawatr ◽

...

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Glucose Uptake ◽

Healthy Subjects ◽

Whole Body ◽

Oral Glucose ◽

Glucose Load ◽

Healthy Humans ◽

Insulin Clamp ◽

Glucose Ingestion

To investigate the effect of elevated plasma free fatty acid (FFA) concentrations on splanchnic glucose uptake (SGU), we measured SGU in nine healthy subjects (age, 44 ± 4 yr; body mass index, 27.4 ± 1.2 kg/m2; fasting plasma glucose, 5.2 ± 0.1 mmol/l) during an Intralipid-heparin (LIP) infusion and during a saline (Sal) infusion. SGU was estimated by the oral glucose load (OGL)-insulin clamp method: subjects received a 7-h euglycemic insulin (100 mU · m−2 · min−1) clamp, and a 75-g OGL was ingested 3 h after the insulin clamp was started. After glucose ingestion, the steady-state glucose infusion rate (GIR) during the insulin clamp was decreased to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in GIR during the period after glucose ingestion from the ingested glucose load. [3-3H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of endogenous glucose production (EGP) and glucose disappearance (Rd). During the 3-h euglycemic insulin clamp before glucose ingestion, Rd was decreased (8.8 ± 0.5 vs. 7.6 ± 0.5 mg · kg−1 · min−1, P < 0.01), and suppression of EGP was impaired (0.2 ± 0.04 vs. 0.07 ± 0.03 mg · kg−1 · min−1, P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly increased during the LIP vs. Sal infusion study (30 ± 2 vs. 20 ± 2%, P < 0.005). In conclusion, an elevation in plasma FFA concentration impairs whole body glucose Rd and insulin-mediated suppression of EGP in healthy subjects but augments SGU.

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Trial of Available Energy Evaluation of Highly Cross-linked Starch and Modified Cellulose Based on Breath H2 Excretion

Current Nutrition & Food Science ◽

10.2174/1573401315666190723145558 ◽

2020 ◽

Vol 16 (5) ◽

pp. 794-801 ◽

Cited By ~ 1

Author(s):

Sadako Nakamura ◽

Kenichi Tanabe ◽

Misa Yamate ◽

Sanae Osada ◽

Tsuneyuki Oku

Keyword(s):

Test Substance ◽

Breath Hydrogen ◽

Simple Method ◽

Stable Suspension ◽

Available Energy ◽

Healthy Humans ◽

Energy Evaluation ◽

Glucose Ingestion ◽

Karaya Gum ◽

Modified Cellulose

Background: The energy value of a substance is essential in nutritional labeling. However, the available energy of newly developed highly cross-linked phosphate starch (HCPS-N) and modified cellulose (MC) are unknown. Objective: To evaluate the available energy of HCPS-N and MC, an indirect and simple method which was applied as an indicator of the fermentability based on the breath hydrogen excretion, was used. Methods: HCPS-N was made from tapioca starch by polymerization in the presence of 0.5% phosphoric acid. MC was made from microcrystalline cellulose, maltodextrin, and karaya gum to attain a highly stable suspension. The present study was carried out using a within-subject, repeatedmeasures design. Blood was collected at 30 min intervals for 3 h after the ingestion of 30 g of a test substance. The end-respiratory gas was collected for 14 h after ingestion of 5 g of a test substance to evaluate the available energy. Results and Discussion: Plasma glucose and insulin levels did not elevate after the ingestion of HCPS-N, although they increased significantly after glucose ingestion. In the experiments to evaluate the available energy, breath hydrogen excretion after ingesting HCPS-N did not increase distinctly during the experiment. Breath hydrogen excretion after preceding HCPS-P (0 kcal) ingestion was also markedly smaller compared with the peak value at 4 h after FOS ingestion. For the ingestion of MC, breath hydrogen excretion increased scarcely, and the basal level remained until the end of the experiment. Conclusion: The available energies were evaluated to be 0 kcal/g for HCPS-N and 1 kcal/g for MC in healthy humans.

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Regulation of Islet Hormone Release and Gastric Emptying by Endogenous Glucagon-Like Peptide 1 after Glucose Ingestion

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2008-0605 ◽

2008 ◽

Vol 93 (12) ◽

pp. 4909-4916 ◽

Cited By ~ 76

Author(s):

Marzieh Salehi ◽

Torsten P. Vahl ◽

David A. D'Alessio

Keyword(s):

Blood Glucose ◽

Gastric Emptying ◽

Glucose Tolerance ◽

Cell Function ◽

Oral Glucose ◽

Glucose Levels ◽

Healthy Humans ◽

Blood Glucose Levels ◽

Glucose Ingestion ◽

Glucagon Like Peptide

Background: Exogenous administration of glucagon-like peptide (GLP)-1 improves glucose tolerance by stimulation of insulin secretion, inhibition of glucagon secretion, and delay of gastric emptying. It is not known which of these effects is involved in the action of endogenous GLP-1 to control blood glucose. To determine the role of endogenous GLP-1 on islet cell function and gastric emptying independent of variable glycemia, we clamped blood glucose before and during glucose ingestion with and without GLP-1 receptor blockade with exendin-[9–39] (Ex-9). Methods: There were 10 healthy subjects that participated in two experiments each, one a control and one with infusion of 750 pm/kg · min Ex-9. Subjects consumed 75 g oral glucose solution mixed with d-xylose and 13C-glucose while their blood glucose levels were held fixed at approximately 8.9 mmol/liter. Results: Plasma insulin levels during hyperglycemia alone were similar in the two studies (control, 282.5 ± 42 vs. Ex-9, 263.8 ± 59 pmol/liter) but were reduced by approximately 30% by Ex-9 after glucose ingestion (control, 1154 ± 203 vs. Ex-9, 835 ± 120 pmol/liter; P < 0.05). Blocking the action of endogenous GLP-1 caused an approximate 80% increase in postprandial glucagon concentrations. The appearance of ingested d-xylose in the blood was not affected by Ex-9, suggesting that postprandial secretion of GLP-1 has only minimal effects on gastric emptying of oral glucose. Conclusions: These findings indicate that GLP-1 is an incretin in healthy humans at modestly supraphysiological blood glucose levels. The primary effect of GLP-1 to regulate oral glucose tolerance is mediated by effects on islet hormones and not on gastric emptying.

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Fasting Decreases the Content ofD-Chiroinositol in Human Skeletal Muscle

International Journal of Experimental Diabetes Research ◽

10.1080/15604280214280 ◽

2002 ◽

Vol 3 (3) ◽

pp. 163-169 ◽

Cited By ~ 5

Author(s):

Pavel N. Shashkin ◽

Laura C. Huang ◽

Joseph Larner ◽

George E. Vandenhoff ◽

Abram Katz

Keyword(s):

Pyruvate Dehydrogenase ◽

Second Messengers ◽

Tolerance Test ◽

Oral Glucose ◽

Dependent Protein Kinase ◽

Healthy Humans ◽

Peripheral Insulin Resistance ◽

Glucose Ingestion ◽

Dependent Protein ◽

Femoris Muscle

Two classes of inositol phosphoglycans have been implicated as second messengers of insulin, one that activates pyruvate dehydrogenase and contains D-chiroinositol, and one that inhibits cyclic AMP–dependent protein kinase and contains myoinositol. We examined the effects of a 3-day fast on muscle contents of inositols in healthy humans. An oral glucose tolerance test was performed and a biopsy was obtained from the quadriceps femoris muscle after an overnight fast and after a 72-hour fast. The 72-hour fast significantly increased plasma glucose (1.5- to 2-fold) and insulin (2- to 4-fold) after glucose ingestion versus the values after the overnight fast, indicating the manifestation of peripheral insulin resistance. The 72-hour fast resulted in an ∼20% decrease in the muscle content of D-chiroinositol (P< 0.02), but no change in the myoinositol content. These data demonstrate that fasting specifically decreases the muscle content of D-chiroinositol in human muscle and this may contribute to the finding that insulin-mediated activation of pyruvate dehydrogenase is attenuated after short-term starvation.

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