Oral Glucose Administration Research Articles

Insulin sensitivity depends on the route of glucose administration

Aims/hypothesisThe small intestine plays an important role in hepatic and whole-body insulin sensitivity, as shown by bariatric surgery. Our goal was to study whether routes and dose of glucose administration have an acute impact on insulin sensitivity. The primary endpoint of this proof-of-concept study was the difference in insulin-mediated metabolic clearance rate (MCR/I) of glucose between the oral and intravenous routes of glucose administration. Secondary endpoints were differences in insulin effect on proteolysis, ketogenesis, lipolysis and glucagon levels.MethodsIn this parallel cohort study, we administered multiple oral glucose loads to 23 participants (aged between 18 and 65 years) with morbid obesity and with normal or impaired glucose tolerance or type 2 diabetes. In a different session, we administered isoglycaemic intravenous glucose infusions (IGIVI) to match the plasma glucose levels observed during the oral challenges. Glucose rate of appearance (Ra) and disappearance (Rd) and endogenous glucose production (EGP) were calculated by infusing [6,6-2H2]glucose with or without oral [U-13C6]glucose. Plasma small polar metabolites were measured by gas chromatography and time-of-flight mass spectrometry. Lipids were measured by ultra-HPLC and quadrupole mass spectrometry. Glucagon-like peptide-1, insulin, C-peptide and glucagon were also measured. Participants, caregivers, people doing measurements or examinations, and people assessing the outcomes were unblinded to group assignment.ResultsGlucose MCR/I was significantly higher during IGIVI than during oral glucose administration, independently of glycaemic status (12 ± 6 for IGIVI vs 7.4 ± 3 ml min−1 kg−1 per nmol/l for oral, p< 0.001 from paired t test). Insulin secretion was higher during oral administration than during IGIVI (p< 0.001). The disposition index was significantly lower during the oral procedure: 4260 ± 1820 vs 5000 ± 2360 (ml min−1 kg−1 (nmol/l)−1 pmol/min; p = 0.005). Insulin clearance was significantly higher when glucose was infused rather than ingested (2.53 ± 0.82 vs 2.16 ± 0.49 l/min in intravenous and oral procedure, respectively, p = 0.006). The efficacy of insulin in inhibiting lipolysis and proteolysis was decreased after oral glucose loads. A heat map diagram showed a different pattern for the metabolites between the two routes of glucose administration.Conclusions/interpretationOur study shows that insulin sensitivity depends on the route of glucose administration, the oral route leading to increased insulin secretion and compensatory insulin resistance compared with the intravenous route. The efficacy of insulin in blocking lipolysis and protein breakdown is lower after oral glucose loads vs the intravenous route. Our findings suggest that, while the glucose-mediated incretin release is followed by an increase in insulin release, the effect of the released insulin is limited by an increase in insulin resistance.Trial registrationClinicalTrials.gov NCT03223129.Graphical abstract

Severe calcium deficiency increased visceral fat accumulation, down-regulating genes associated with fat oxidation, and increased insulin resistance while elevating serum parathyroid hormone in estrogen-deficient rats

Menopause impairs calcium(Ca) metabolism and reduces bone mineral density (BMD), but the interaction of menopause with Ca deficiency in energy, glucose, lipid, and bone metabolism has not been studied. Herein we hypothesized that Ca deficiency at levels for post-menopausal women would impair energy, glucose, lipid, and bone metabolism in estrogen-deficient rats. This hypothesis was examined in ovariectomized (OVX) rats fed high-fat diets with different Ca levels for 12 weeks. OVX rats were allocated into either very low Ca (0.02%, VLCA), low Ca (0.7%, LCA), adequate Ca (1.18%, ACA, control), or excessive Ca (2.1%, EXCA). Sham-operated rats had the same diet as ACA (Normal-control). Ca intake was 37, 107, 190, and 311 mg/kg bw/d in the VLCA, LCA, ACA, and EXCA groups. The ACA group had higher serum parathyroid hormone concentrations than the Normal-control but were highest in VLCA. VLCA decreased BMD and lean body mass compared to ACA. Fasting serum glucose concentrations, even with higher serum insulin concentrations, were higher in the VLCA than ACA, indicating increased insulin resistance in VLCA. VLCA deteriorated glucose tolerance after oral glucose administration and impaired lipid profiles. LCA and EXCA had similar effects on metabolism as ACA, but LCA did not improve insulin sensitivity and lipid profiles as much as ACA. Expressions of hepatic genes related to fatty acid and cholesterol synthesis (FAS and SREBP-1c and HMGCR) were much higher in the VLCA than ACA and expressions of genes related fatty acid degradation(CPT1 and CYP7A1) were much lower in VLCA than ACA. In conclusion, we accepted the hypothesis. Very low Ca intake (350–400 mg/d as a human equivalent) exacerbated estrogen-deficiency-induced impairments of energy, glucose, and lipid metabolism by elevating serum parathyroid hormone levels and inducing visceral fat accumulation and insulin resistance in estrogen-deficient rats, but there was no added benefit of excessive Ca.

Effect of acrylamide on glucose homeostasis in female rats and its mechanisms

Acrylamide (AA), a food contaminant, caused islet remodeling and increased hepatic glycogen content in male rats, but the effect of AA on glucose homeostasis in female rats remains unclear. In this study, female SD rats were orally treated with 0, 15, or 30 mg/kg·bw AA for 3 weeks. The levels of fasting blood glucose (FBG), blood glucose after oral administration of glucose, plasma insulin and hepatic glycogen were measured. The histology of the pancreas was observed, and the transcription of key genes involved in glucose metabolism and insulin signaling in liver were determined. Compared with the control, exposure to 30 mg/kg·bw of AA significantly increased FBG level, reduced hepatic glycogen content and impaired glucose tolerance. Moreover, damaged islets were observed at 15 and 30 mg/kg·bw AA-exposed groups. In addition, AA exposure significantly promoted gluconeogenesis and glycogenolysis (up-regulation of pc, g6p and gp) and decreased glycolysis (down-regulation of gck and pfk). Alternations in these processes may be associated with decreased plasma insulin levels and inhibited insulin-regulated IRS/PI3K/Akt/Foxo1 signaling transduction under AA exposure. Overall, our findings demonstrated that AA disrupted glucose homeostasis and elevated FBG level in female rats possibly by interfering with glucose metabolism and hampering the physiological effect of insulin.

Inhibitory Effect of Ocimum gratissimum Leaf Extract on Postprandial Increase of Blood Glucose

The tea of Ocimum gratissimum (OG) leaves has been commonly consumed by people living in Ishigaki Island, Okinawa prefecture, Japan, and is considered to be effective for improving diabetes mellitus. In this study, we aimed to clarify the inhibitory potential of OG leaves extract (OG-ext) on gastrointestinal glucose absorption and to provide theoretical evidence for the anti-hyperglycemic effect of OG-ext. The increase of blood glucose after oral administration of α-starch and glucose in mice was suppressed by co-administration of OG-ext. An in vitro enzymatic assay suggested that amylase and maltase were inhibited weakly by the addition of OG-ext. In Caco-2 cells, a human intestinal epithelial model, the sodium-dependent glucose transporter (SGLT) 1-mediated uptake of fluorescence glucose analog was inhibited significantly by the addition of OG-ext in a concentration-dependent manner. These results indicate that the inhibitory effect on SGLT1 is one of the mechanisms of the anti-hyperglycemic effect of the tea of OG leaves.

Fructose tolerance test in obese people with and without type 2 diabetes

Fructose is distinct among common sugars in its ability to raise serum uric acid, and some studies suggest fructose-induced uric acid production may have a role in the ability of this sugar to induce metabolic syndrome. A fructose tolerance test has been previously developed to evaluate the relative ability of fructose to raise uric acid in individuals. However, the effect of fructose to raise uric acid in people with diabetes has not been studied. People with type 2 diabetes (n = 143) and without diabetes controls (n = 132) with similar body mass index (BMI) underwent an oral fructose tolerance test. As a comparison, participants also had their uric acid levels measured after an oral glucose tolerance test on a different day. Serum uric acid was lower in people with type 2 diabetes compared to controls with a similar BMI, especially those with poor glucose control (glycosylated hemoglobin [HbA1c] ≥ 8%). Fructose administration raised serum uric acid in both groups, with a lower absolute rise in people with diabetes. People with diabetes with a blunted rise in serum uric acid had higher baseline serum uric acid concentrations and a higher BMI. People without diabetes with a higher BMI also showed a blunted serum uric acid response. Oral glucose administration lowered serum uric acid in both participants, with a greater fall in those with diabetes. Both the presence of diabetes and obesity blunt the serum uric acid response to fructose ingestion. These data demonstrate altered fructose-dependent urate metabolism in type 2 diabetes.

Expression of glut2 in response to glucose load, insulin and glucagon in grass carp (Ctenophcuyngodon idellus).

Generally, fish are thought to have a limited ability to utilize carbohydrate. Postprandial blood glucose is cleared sluggishly in fish, resulting in prolonged hyperglycemia. Facilitative glucose transporters (GLUTs) play an important role in glucose utilization. In the present study, the expression levels of glut2 in different tissues were detected in grass carp. Furthermore, the effects of oral glucose administration on glut2 mRNA expression in the liver, intestine and kidney were investigated, and we also evaluated the response of glut2 mRNA to insulin and glucagon in the primary hepatocytes of grass carp. The expression level of glut2 mRNA was highest in the liver, followed by the intestine and kidney, but lower in other tissues. The result of glucose tolerance test (GTT) showed that serum glucose reached the highest level at 3 h after GTT and recovered to the basic level at 6 h. The glut2 mRNA in the intestine was up-regulated at 1 h after GTT. However, the glut2 mRNA expression in the liver of grass carp was unchanged after GTT for 1, 3, 6 h, and even decreased at 12 h after GTT. In addition, the expression of glut2 mRNA in the primary hepatocytes was enhanced by insulin and glucagon at 3 h post treatment. These results suggested that glut2 expression in the liver of grass carp was sensitive to insulin and glucagon, but not blood glucose. The up-regulation of glut2 by these hormones might be involved in the bi-directional transportation of glucose in the liver.

Effect of portal glucose sensing on incretin hormone secretion in a canine model.

It is unknown whether activation of hepato-portal vein (PV) glucose sensors plays a role in incretin hormone amplification of oral glucose-stimulated insulin secretion (GSIS). In previous studies, PV glucose infusion increased GSIS through unknown mechanisms, perhaps neural stimulation of pancreatic β-cells and/or stimulation of gut incretin hormone release. Thus, there could be a difference in the incretin effect when comparing GSIS with portal rather than leg vein (LV) glucose infusion. Plasma insulin and incretin hormones were studied in six overnight-fasted dogs. An oral glucose tolerance test (OGTT) was administered, and then 1 and 2 wk later the arterial plasma glucose profile from the OGTT was mimicked by infusing glucose into either the PV or a LV. The arterial glucose levels were nearly identical between groups (AUCs within 1% of each other). Oral glucose administration increased arterial GLP-1 and GIP levels by more than sixfold, whereas they were not elevated by PV or LV glucose infusion. Oral glucose delivery was associated with only a small incretin effect (arterial insulin and C-peptide were 21 ± 23 and 24 ± 17% greater, respectively, during the 1st hour with oral compared with PV glucose and 14 ± 37 and 13 ± 35% greater, respectively, in oral versus LV; PV versus LV responses were not significantly different from each other). Thus, following an OGTT incretin hormone release did not depend on activation of PV glucose sensors, and the insulin response was not greater with PV compared with LV glucose infusion in the dog. The small incretin effect points to species peculiarities, which is perhaps related to diet.

The impact of sex hormones and metabolic markers on depressive symptoms and cognitive functioning in PCOS patients

The aim of the study was to analyze associations between cognitive deficits and such factors like hormone levels and metabolic risk factors in PCOS women. Fifty-five PCOS patients aged 17–30 underwent analyses for FSH, LH, 17-beta-estradiol, DHEAS, androstenedione, SHBG, lipid profile during the follicular phase. Fasting glucose and insulin concentrations were also measured, as well as their levels after oral-glucose administration. All participants underwent an assessment with: Trail Making Test A and B, Stroop Test, Verbal and Categorical Fluency Test. The intensity of depressive symptoms was measured by the Beck Depression Inventory (BDI). We observed a positive correlation of the depression scores with the OGTT 120′ and triglycerides, and a negative correlation of the depression scores with serum HDL. The higher were the insulin levels at 120 min; the more pronounced were the deficits of the verbal psychomotor speed. Higher free testosterone correlated with better verbal psychomotor speed. Androstenedione level was associated with worse scores in executive functions assessment. 17-OH-P levels positively correlated with phonology verbal fluency scores and higher plasma cortisol level at 10 p.m. correlated with worse verbal processing speed. Endocrine and metabolic parameters seem to be important factors mediating cognitive deficits in PCOS.

First aid glucose administration routes for symptomatic hypoglycaemia.

First aid glucose administration routes for symptomatic hypoglycaemia.

First aid glucose administration routes for symptomatic hypoglycaemia

First aid glucose administration routes for symptomatic hypoglycaemia

Molecular and functional characterization of sirt4 and sirt6 in Megalobrama amblycephala under high glucose metabolism

We analyzed the sequences of sirt4 and sirt6 and their changes in expression after oral glucose administration in blunt snout bream (Megalobrama amblycephala). We cloned sirt4 and sirt6 and found that their full-length cDNA sequences were 1530 bp and 1723 bp, respectively; their amino acid sequences were 93% and 92% identical to Danio rerio. Megalobrama amblycephala were fed a high glucose solution (3 g/kg). Normally, sirt4 expression is higher in spleen, intestine, and gill (P < .05), and sirt6 expression is higher in intestine and gill (P < .05). After oral glucose administration, sirt4 and sirt6 expression increased in liver and gill, and sirt4 expression increased in intestine at 0.5 h (P < .05). In contrast, sirt4 in kidney and sirt6 in head kidney were downregulated at 1 h (P < .05). Expression of sirt4 was upregulated in brain, head kidney, spleen, muscle, and liver 2 h, 4 h, 4 h/24 h, 8 h, and 24 h, respectively (P < .05). Expression of sirt4 was downregulated in kidney at 8 h-48 h (P < .05). Expression of sirt6 was upregulated in intestine, liver, muscle, kidney, and spleen at 4 h/24 h, 8 h/24 h, 12 h, 12 h, and 24 h, respectively (P < .05). We report that sirt4 and sirt6 are highly conserved in evolution and exhibit tissue-specific expression profiles. We demonstrate that the expression of sirt4 and sirt6 are tissue-specific, and depend upon tissue-specific responses to glucose metabolism.

Perioperative management in a patient with type 1 diabetes mellitus who presented severe hypoglycemia during dental implant surgery: a case report

BackgroundPatients with type 1 diabetes mellitus (DM) have poor glycemic control owing to extreme impairments in glucose tolerance. There are few reports regarding dental implant surgery in patients with type 1 DM. We describe herein the perioperative glycemic management in an outpatient with type 1 DM who experienced a rare case of severe hypoglycemia during dental implant surgery. Only one such case has previously been reported.Case presentationA 60-year-old male patient diagnosed with type 1 DM was scheduled for dental implant primary surgery. Premedication with peroral antibiotics was carried out to prevent possible systemic infection as a complication of DM. The patient was treated to control intraoperative hypertension with diligent attention to cardiovascular conditions by using a bolus administration of nicardipine and diltiazem. During surgery, he abruptly complained of hypoglycemic symptoms and had a blood glucose level of 32 mg/dL. Following oral administration and electrolyte-combined infusion of glucose, he immediately recovered from the critical situation. The surgical procedure, involving a lower jaw implant fixture placement, was performed as planned and resulted in less invasion, limited to the area of implant fixture placement within the right mandibular region of the two molars, compared to implant surgery that spans the entire lower jaw.ConclusionsThe present case suggests that it is essential to promptly monitor possible signs of hypoglycemia-precipitated acute symptoms in patients with DM. In addition, it is also necessary to appropriately administer insulin with an electrolyte-combined infusion of glucose for deliberate glycemic control; this is particularly true in patients with type 1 DM undergoing relatively highly-invasive oral surgical manipulation such as commonly performed dental implant surgery spanning the entire jaw.

Clinical Characteristics of Acromegalic Patients With Paradoxical GH Response to Oral Glucose Load.

A paradoxical GH response to oral glucose (OG) is often found in acromegaly. However, the clinical characteristics of patients with acromegaly and a paradoxical GH response to OG (OG responders) remain unclear. The aim of the present study was to define the clinical characteristics of OG responders with acromegaly. Retrospective study. Hospitalized care at Osaka University Hospital. Of 63 patients with acromegaly admitted to our hospital from January 2006 to January 2017, 19 were classified as OG responders and 44 as nonresponders. The clinical characteristics of these groups were compared. Before surgery, OG responders had substantially greater IGF-1 SD scores than nonresponders (P < 0.05), although no difference was found in basal GH levels between the two groups (P = 0.46). Regarding glucose metabolism, 120-minute plasma glucose and immunoreactive insulin after OG administration and hemoglobin A1c were significantly greater in OG responders than in nonresponders (P < 0.01, P < 0.05, P < 0.05, respectively). GH levels during octreotide or bromocriptine testing were decreased more significantly in OG responders than in nonresponders (P < 0.05, P < 0.05, respectively). The proportion of pituitary tumors with hypointensity on T2-weighted MRI was significantly greater in OG responders than in nonresponders (P < 0.05). The difference in IGF-1 and parameters of glucose metabolism described disappeared between the two groups after surgery. The paradoxical GH response reflected the clinical characteristics, especially IGF-I level, glucose metabolism, and drug efficacy in acromegaly. A paradoxical GH response, in addition to the nadir GH levels, to OG load is potentially useful for evaluation of the clinical characteristics of acromegaly.

Laser Acupuncture on LI 4 Compared with Oral Glucose Administration for Pain Prevention in Healthy Term Neonates Undergoing Routine Heel Lance

Laser Acupuncture on LI 4 Compared with Oral Glucose Administration for Pain Prevention in Healthy Term Neonates Undergoing Routine Heel Lance

Adverse Impact of Hashimoto's Thyroiditis on Pancreatic Beta-Cell Function in Type 2 Diabetic Patients

Background: Hashimoto’s thyroiditis (HT) is an autoimmune disease and often complicated with other metabolic disorders. It has been shown that HT patients have higher levels of antibodies against proinsulin than controls. The incidence of HT in T2DM patients is unclear and has never been studied whether beta cell function differ between T2DM patients alone and complexed with HT. Methods: 8T2DM patients who were recruited between November 2015 till June 2016 to Endocrinology Center in Lu He hospital were analyzed. HT was diagnosed if either serum TPO antibody or TG antibody exceeded the normal range. After a 12-hour overnight fast, venous blood samples were obtained to measure total cholesterol, triglyceride, HDL-c, FBG, insulin and Scr. Oral glucose tolerance test (OGTT) was examined in the patients and serum c-peptide levels were quantified at 0, 1, 2, and 3 hours after glucose administration. Results: 8T2DM patients were included in the study. 249 patients were diagnosed HT.Compared with non-HT subjects, T2DM with HT were more males (44.7% vs. 35.2%, p=0.02) and had higher values of systolic blood pressure (133.8 mm Hg vs. 131.1 mmHg, p=0.03). Although age, body mass index, HbA1c, serum cholesterol and serum triglyceride did not differ between two groups (p≥0.17 for all), fasting C-peptide levels were lower in T2DM complicated with HT than T2DM alone (1.09 ±0.90 nmol/L vs. 1.28±0.98 nmol/L, p=0.004). To further compare beta cell function, patients were performed OGTT test. Serum C-peptide levels remained lower at 1 and 2 hours after oral administration of 75-g glucose in T2DM with HT than T2DM alone (1 hour: 2.10±1.77 nMol/L vs. 2.33 ±1.84 nMol/L, p=0.03; 2 hours: 3.04±2.56 vs. 3.47±2.77 nmol/L, p=0.02). Serum C-peptide levels were comparable three hours after 75-g glucose intake (3.16±2.45 nmol/L vs. 3.50±2.78 nMol/L, p=0.49). Conclusion: The prevalence of HT is relatively high in T2DM patients, which was associated with reduced beta cell function. Disclosure Y. Zhang: None. R. Sun: None. L. Zhang: None. Y. Fang: None. C. Yu: None. S. Yuan: None. Y. Feng: None. D. Zhao: None.

Incretin Hormone Release Does Not Involve Hepatic Portal Vein Glucose Sensors

The incretin effect, which is defective in individuals with T2D, involves the secretion of GLP-1 and GIP when glucose is given orally, but not when it is infused via a peripheral vein. Glucose ingestion results in a hepatic portal vein/arterial glucose gradient. This activates portal vein glucose sensors which play an important role in the regulation of glucose metabolism during feeding. It is unknown whether these sensors contribute to GLP-1 or GIP secretion during glucose ingestion. To test the hypothesis that portal but not peripheral vein glucose infusion would stimulate incretin hormone secretion, intraportal (infusion) and femoral artery (sampling) catheters were placed in 6 dogs. Two weeks later the animals were administered an oral glucose tolerance test (OGTT; 0.9 g/kg) and one and two weeks after that the arterial plasma glucose profile which occurred during each OGTT was matched by infusing glucose either into the portal (Po) or a peripheral (Pe) vein. The AUCs for glucose (0-180 min; total) were nearly identical: 8251±325, 8219±334 and 8200±341 mg/dl (180 min) in the OGTT, Po and Pe treatments, respectively. The total glucose administered was reduced in the Pe (562±76 mg/kg) compared to the OGTT and Po treatments (900±0 and 856±92 mg/kg, respectively). During the 1st hour the arterial insulin and c-peptide responses were ∼25% greater in the OGTT compared to the other treatments, whereas there was &amp;lt;5% difference in their levels in Po vs. Pe. Arterial glucagon fell modestly in all treatments. Oral glucose administration increased arterial GLP-1 and GIP levels by &amp;gt;6-fold over basal, but their levels did not change in Po or Pe. The 0-180 min AUCs for GLP-1 were 669±218, 315±128 and 323±81 pg/ml, and for GIP were 14725±1506, 2556±529 and 2658±316 pg/ml in the OGTT, Po and Pe treatments, respectively. Thus, activation of portal vein glucose sensors did not stimulate the release of, or insulinotropic response to, incretin hormones in the overnight fasted dog, but portal vein glucose entry enhanced glucose clearance. Disclosure D.S. Edgerton: Speaker's Bureau; Self; Novo Nordisk A/S. G. Kraft: None. M.S. Smith: None. L. Moore: None. B. Farmer: None. H. Sara: None. M. Scott: None. M. Moore: None. M.A. Nauck: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Fractyl Laboratories, Inc., GlaxoSmithKline plc., Berlin-Chemie AG, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Berlin-Chemie AG, Merck Sharp &amp; Dohme Corp., Medscape, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Berlin-Chemie AG, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, GlaxoSmithKline plc., Novo Nordisk A/S. Consultant; Self; Nordic Bioscience, Empros. A.D. Cherrington: Advisory Panel; Self; Biocon. Consultant; Self; Boston Scientific Corporation. Research Support; Self; Boston Scientific Corporation. Consultant; Self; Eli Lilly and Company. Advisory Panel; Self; Fractyl Laboratories, Inc.. Stock/Shareholder; Self; Fractyl Laboratories, Inc.. Consultant; Self; Galvani Bioelectronics Limited. Research Support; Self; Galvani Bioelectronics Limited. Consultant; Self; MedImmune. Advisory Panel; Self; Metavention. Stock/Shareholder; Self; Metavention. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Advisory Panel; Self; NuSirt Biopharma, Inc., Sensulin Labs, LLC.. Other Relationship; Self; Sensulin Labs, LLC.. Consultant; Self; Silver Lake. Research Support; Self; Silver Lake. Consultant; Self; Thermalin Diabetes, LLC., Thetis Pharmaceuticals LLC.. Stock/Shareholder; Self; Thetis Pharmaceuticals LLC.. Advisory Panel; Self; VTV Therapeutics. Consultant; Self; VTV Therapeutics. Advisory Panel; Self; Zafgen. Research Support; Self; Zafgen. Stock/Shareholder; Self; Zafgen. Consultant; Self; Abvance. Other Relationship; Self; Abvance. Consultant; Self; California Institute for Biomedical Research (Calibr). Advisory Panel; Self; These Three Medical, Inc (T3M).

Chronic oscillating glucose challenges disarrange innate immune homeostasis to potentiate the variation of neutrophil-lymphocyte ratio in rats with or without hidden diabetes mellitus.

BackgroundThe neutrophil–lymphocyte ratio (NLR) has been considered as an inflammatory marker in various disorders, but it is not clear whether the NLR is also elevated with hidden diabetes (HD), which is normal in fasting blood glucose (FBG) but abnormal in the oral glucose tolerance test (OGTT).Materials and methodsAn HD animal model for 27 days and an animal model with oscillating glucose (OG) for 7 days were applied on adult female Sprague–Dawley rats. OGTT, leukogram analysis, histology, and immunohistochemistry were carried out.ResultsIn HD rats, the percentage of neutrophils increased but the percentage of lymphocytes decreased; hence, the NLR rose relative to sham. This may be a result of the OG levels often experienced by diabetic subjects, as normal rats given OG (6 g/kg/6 h) for 7 days had significantly reduced lymphocyte numbers and increased NLR compared with the values before and 1 h after oral glucose administration during OGTT. Glucose-induced disarrangement of partitions of circulating immune cells and NLR was involved in the increase in oxidative stress, as these changes were totally blocked by the antioxidant glutathione (GSH). GSH (50 mg/kg/6 h) totally blocked the glucose-induced alterations in lymphocyte and NLR values.ConclusionHD associated with elevation of NLR values may be partly attributed to a homeostasis disorder of the innate inflammatory state, caused by oscillating hyperglycemia. Acute high glucose administration produced a significant decrease in lymphocyte number. OG administration potentiated this effect and increased the NLR value, which was blocked by GSH, suggesting that reactive oxygen species play a critical role in maintaining lymphocyte numbers.

Comparatively study on the insulin-regulated glucose homeostasis through brain-gut peptides in Japanese flounder Paralichthys olivaceus after intraperitoneal and oral administration of glucose

The present study comparatively analyzed the blood glucose and insulin concentration, the temporal and spatial expression of brain-gut peptides and the key enzymes of glycolysis and gluconeogenesis in Japanese flounder by intraperitoneal injection (IP) and oral administration (OR) of glucose. Samples were collected at 0, 1, 3, 5, 7, 9, 12, 24 and 48 h after IP and OR glucose, respectively. Results showed that the hyperglycemia lasted for about 10 h and 21 h in OR and IP group, respectively. The serum insulin concentration significantly decreased at 3 h (1.58 ± 0.21 mIU/L) after IP glucose. However, it significantly increased at 3 h (3.37 ± 0.341 mIU/L) after OR glucose. The gene expressions of prosomatostatin, neuropeptide Y, cholecystokinin precursor and orexin precursor in the brain showed different profiles between the OR and IP group. The OR not IP administration of glucose had significant effects on the gene expressions of preprovasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide and gastrin in intestine. In conclusion, brain-gut peptides were confirmed in the present study. And the serum insulin and the brain-gut peptides have different responses between the IP and OR administration of glucose. The OR could stimulate the brain-gut peptide expressions, which have effects on the insulin secretion and then regulate the blood glucose levels. However, in IP group, there is little chance to stimulate brain-gut peptide expression to influence the insulin secretion, which leads to a longer hyperglycemia.

Esophagus-duodenum Gastric Bypass Surgery Improves Glucose and Lipid Metabolism in Mice

BackgroundDespite of its significant therapeutic effects on obesity and metabolic diseases, Roux-en-Y gastric bypass (RYGB) has limited clinical application because of considerable impacts on the gastrointestinal structure and postoperative complications. This study aims to develop a simplified surgical approach with less damage and complication but efficient metabolic benefit. MethodsThe effects of Esophagus-Duodenum gastric bypass (EDGB) on body weight, food intake, glucose and lipid metabolism were compared to RYGB in mice. FindingsEDGB is simple, has higher survival rate and less complication. Relative to RYGB, EDGB demonstrated modest body weight control, identical improvement of glucose and lipid metabolism in obese mice. Blood glucose increased significantly 15 and 30min after oral glucose administration, then markedly decreased in both EDGB and RYGB groups relative to the sham surgery, indicating a quicker absorption of oral glucose and improvement in glucose uptake by insulin targeted tissues. Insulin sensitivity was identically improved. EDGB significantly decreased plasma and hepatic triglyceride levels, while increased browning in visceral and subcutaneous white adipose tissue to the extent identical to RYGB. Levels of ghrelin and nesfatin-1 increased significantly after EDGB and RYGB. InterpretationEDGB is a valuable model to study the metabolic benefit of bariatric surgery in mice.

Laser Acupuncture at Large Intestine 4 Compared with Oral Glucose Administration for Pain Prevention in Healthy Term Neonates Undergoing Routine Heel Lance: Study Protocol for an Observer-Blinded, Randomised Controlled Clinical Trial.

Background Nonpharmacological strategies have actually become more important in neonatal pain management during routinely applied minor painful procedures. However, commonly used nonpharmacological strategies are inferior to orally administered sweet solutions. Therefore, we will compare laser acupuncture, as a recent nonpharmacological method, with the standard care of oral glucose solution for pain prevention. Methods Ninety-five healthy term neonates will be allocated into one of two groups. Before routine heel lance for metabolic screening, one group will receive laser acupuncture at acupuncture point Large Intestine 4 (LI 4) bilaterally for 60 seconds per point (acupuncture group) and the other will receive the standard care with orally administered glucose solution (glucose group). The complete procedure of blood sampling will be recorded on video, excluding the intervention before heel lance. A paediatric nurse, blinded with respect to the allocation, will evaluate these video recordings and determine the Premature Infant Pain Profile (PIPP) for each neonate. Primary outcome will be the mean difference in PIPP scores between groups. Discussion This observer-blinded randomised controlled trial has been designed to explore potential advantages of laser acupuncture in the management of neonatal pain because more data are required to provide information about its efficacy and safety. Trial Registration This trial is registered with DRKS00010122.