Reductions In Postprandial Glucose Levels Research Articles

The Rate of Glucose Appearance Is Related to Postprandial Glucose and Insulin Responses in Adults: A Systematic Review and Meta-analysis of Stable Isotope Studies

It is often assumed that lower postprandial glucose (PPG) and insulin (PPI) responses are induced by slower glucose influx from the gut (e.g., by delayed carbohydrate digestion). However, changes in the rate of appearance of glucose in the peripheral circulation [rate of appearance of exogenous glucose (RaE)] may be accompanied by changes in endogenous glucose production (EGP) and the rate of disappearance of total glucose into tissues (RdT). The quantitative relationships between reductions in RaE and PPG/PPI levels are unclear. The objective was to perform a meta-analysis to quantify the effect of changes in RaE on changes in PPG and PPI levels (primary) and EGP and RdT (secondary). We systematically searched the Scopus, Medline, and Cochrane library databases through 10 January 2019 for randomized, controlled, carbohydrate-rich interventions that aimed to reduce RaE in humans, measured using dual or triple stable isotope methods. The 2-h net incremental AUCs for all variables were extracted or calculated. Relationships between RaE and outcomes were quantified by weighted regression analyses. There were 12 articles, including 17 comparisons, that satisfied the inclusion criteria. The subjects were mainly men (60%), with age and BMI ranges of 18-40 y and 20.0-27.5 kg/m2, respectively. A 10% reduction in RaE was associated with reductions in PPG levels, PPI levels, and the RdT of 7% (95% CI: 2%, 12%; P=0.010), 8% (95% CI: 2%, 13%; P=0.012), and 11% (95% CI: 4%, 17%; P=0.005), respectively, but was not significantly associated with a change in EGP (13%; 95% CI: -7%, 33%; P=0.176). All fluxes together explained 70% and 26% of the variances in PPG and PPI levels, respectively. In adults, reducing glucose RaE by diet is associated with significant reductions in PPG levels, PPI levels, and the rate of glucose disposal. This trial was registered in the PROSPERO database with identifier CRD42018084824.

Randomised, phase 1, dose-finding study of MEDI4166, a PCSK9 antibody and GLP-1 analogue fusion molecule, in overweight or obese patients with type 2 diabetes mellitus

Aims/hypothesisCardiovascular disease is the leading cause of morbidity and mortality in people with type 2 diabetes. MEDI4166 is a proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody and glucagon-like peptide-1 (GLP-1) analogue fusion molecule designed to treat patients with type 2 diabetes who are at risk for cardiovascular disease. In this completed, first-in-human study, we evaluated the safety and efficacy of single or multiple doses of MEDI4166 in participants with type 2 diabetes.MethodsIn this phase 1 study that was conducted across 11 clinics in the USA, eligible adults had type 2 diabetes, a BMI of ≥25 kg/m2 to ≤42 kg/m2, and LDL-cholesterol levels ≥1.81 mmol/l. Participants were randomised 3:1 to receive MEDI4166 or placebo using an interactive voice/web response system, which blinded all participants, investigators and study site personnel to the study drug administered. In ‘Part A’ of the study, five cohorts of participants received a single s.c. injection of MEDI4166 at 10 mg, 30 mg, 100 mg, 200 mg or 400 mg, or placebo. ‘Part B’ of the study consisted of three cohorts of participants who received an s.c. dose of MEDI4166 once weekly for 5 weeks at 50 mg, 200 mg or 400 mg, or placebo. The primary endpoint in Part A was safety. The co-primary endpoints in Part B were change in LDL-cholesterol levels and area under the plasma glucose concentration–time curve (AUC0–4h) post-mixed-meal tolerance test (MMTT) from baseline to day 36. The pharmacokinetics and immunogenicity of MEDI4166 were also evaluated.ResultsMEDI4166 or placebo was administered to n = 30 or n = 10 participants, respectively, in Part A of the study, and n = 48 or n = 15 participants, respectively, in Part B. The incidence of treatment-emergent adverse events (TEAEs) were comparable between MEDI4166 and placebo in both Part A (60% vs 50%) and Part B (79% vs 87%) of the study. Common TEAEs with MEDI4166 included injection-site reactions, diarrhoea and headache; there was no evidence for dose-related increases in TEAEs. In Part B of the study, at all tested doses of MEDI4166, there was a significant decrease in LDL-cholesterol levels vs placebo (least squares mean [95% CI]; MEDI4166 50 mg, −1.25 [−1.66, −0.84]; MEDI4166 200 mg, −1.97 [−2.26, −1.68]; MEDI4166 400 mg, −1.96 [−2.23, −1.70]; placebo, −0.03 [−0.35, 0.28]; all p < 0.0001). However, there were no clinically relevant reductions or significant differences between MEDI4166 vs placebo in glucose AUC0–4h post-MMTT (least squares mean [95% CI]; MEDI4166 50 mg, −10.86 [−17.69, −4.02]; MEDI4166 200 mg, −4.23 [−8.73, 0.28]; MEDI4166 400 mg, −2.59 [−7.14, 1.95]; placebo, −4.84 [−9.95, 0.28]; all p > 0.05). MEDI4166 was associated with a pharmacokinetic profile supportive of weekly dosing and an overall treatment-induced anti-drug antibody-positive rate of 22%.Conclusions/interpretationMEDI4166 was associated with an acceptable tolerability profile and significantly decreased LDL-cholesterol levels in a dose-dependent manner in overweight or obese patients with type 2 diabetes. However, there were no significant reductions in postprandial glucose levels at any dose of MEDI4166.Trial registrationClinicalTrials.gov NCT02524782FundingThis study was funded by MedImmune LLC, Gaithersburg, MD, USA.

Efficacy and Safety of Teneligliptin in Indian Patients with Inadequately Controlled Type 2 Diabetes Mellitus: A Randomized, Double-blind Study.

Aims:This study evaluated the efficacy and safety of teneligliptin in patients with inadequately controlled type 2 diabetes mellitus (T2DM).Settings and Design:This was a randomized, doubleblind, placebocontrolled, parallelgroup, multicenter, Phase III study.Subjects and Methods:Patients with T2DM and inadequate glycemic control (glycosylated hemoglobin [HbA1c]: >7.0-≤8.5%) were enrolled. Patients were randomly assigned (ratio: 2:1) to receive teneligliptin 20 mg (Glenmark) or placebo. The primary efficacy variable was change from baseline in HbA1c at week 16. Additional analyses included the proportion of patients who achieved target of HbA1c ≤7.0%, changes in fasting plasma glucose (FPG), and postprandial glucose (PPG).Statistical Analysis:Mean change in HbA1c was analyzed using an analysis of covariance model, least square (LS) means, 95% confidence intervals (CIs), and P values were calculated.Results:Overall, 237 patients were included. Patients of the teneligliptin group showed reduced HbA1c levels (LS mean difference = −0.304% for intent-to-treat [ITT]; −0.291% for per-protocol (PP) populations) after 16 weeks of treatment, and a statistically significant difference was observed between the ITT (LS mean difference = 0.555; 95% CI: 0.176–0.934; P = 0.0043) and PP populations (LS mean difference = 0.642; 95% CI: 0.233–1.052; P = 0.0023). Target HbA1c level was achieved by a greater proportion of teneligliptin group patients (ITT, 43.4%; PP, 43.6%) than placebo group patients (ITT, 27.3%; PP, 26.6%). Reduction in FPG levels was observed in ITT (LS mean difference: 8.829; 95% CI: −4.357–22.016; P = 0.1883) and PP populations (LS mean difference: 11.710 mg/dL; 95% CI: −2.893-26.312; P = 0.1154). Reduction in PPG levels was higher in teneligliptin group than placebo group in both ITT (LS mean difference = 25.849 mg/dL; 95% CI: 7.143–44.556; P = 0.0070) and PP populations (LS mean difference = 25.683 mg/dL; 95% CI: 5.830–45.536; P = 0.0115). Overall, 44 patients (18.6%) experienced at least one adverse event. Three or more hypoglycemic events were experienced by 2.5% patients of teneligliptin group and none in placebo group.Conclusion:Treatment with once-daily teneligliptin led to statistically significant and clinically meaningful reductions in HbA1c and PPG, and was well tolerated in Indian patients with T2DM.

Divided consumption of late-night-dinner improves glucose excursions in young healthy women: A randomized cross-over clinical trial

AimsOur aim was to explore the acute effect of the late-night-dinner and the divided-dinner on postprandial glucose levels in young healthy women. MethodsFourteen women (22.6 ± 2.6 years, BMI 20.2 ± 1.5 kg/m2: mean ± SD) were randomly assigned to this crossover study. Each participant wore a continuous glucose monitor for 5 days and consumed identical test meals from the second to the fourth day at home. Each participant consumed the test meals of breakfast at 0800 h, lunch at 1300 h, and the half of the participants consumed dinner at 2100 h (D21) on the second day, 1800 h (D18) on the third day, and divided dinner (DD: vegetable and rice at 1800 h, and vegetable and the main dish at 2100 h) on the fourth day. The rest of the participants consumed DD on the second day, and D21 on the fourth day. ResultsD21 demonstrated higher incremental glucose peak (IGP 2.74 ± 0.38 vs. 1.57 ± 0.23 mmol/L, p < .05, mean ± SEM) and incremental area under the curve for glucose (IAUC) 2300–0800 h (271 ± 63 vs. 111 ± 37 mmol/L × min, p < .05) than D18. On the other hand, DD ameliorated IGP (1.96 ± 0.29 mmol/L, p < .05), IAUC 2300–0800 h (80 ± 29 mmol/L × min, p < .001), and the mean amplitude of glycemic excursion (DD 2.34 ± 0.25 vs. D21 2.91 ± 0.28 mmol/L, p < .05) than D21. ConclusionsConsuming late-night-dinner increased postprandial glucose levels, compared to DD, suggesting DD could be a practical strategy for reduction of postprandial glucose levels in young healthy women.

Incretin secretion and glucose metabolism in morbidly obese patients in the early and late periods after biliopancreatic diversion

To estimate the parameters of glucose metabolism and to assess the secretion of incretins in patients after biliopancreatic diversion (BPD) for morbid obesity (MO) in the early and late postoperative periods. The prospective part of the investigation included 22 patients with a body mass index of 35.8 to 68.4 kg/m2 and type 2 diabetes mellitus (T2DM). All the patients were examined before, 3 weeks and 3 months after BPD. The retrospective part covered 23 patients who were examined after BPD for MO; the postoperative period was 4.7 [2.3; 7.2] years. A control group consisted of 22 healthy, normal weight volunteers. A 75-g oral glucose tolerance test was carried out in all the groups to study the levels of glucose, immunoreactive insulin (IRI), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon at 0, 30, 60, and 120 min. T2DM patients showed improvement in glucose metabolism just 3 weeks after BPD; following 3 months, they had normalized fasting blood glucose levels (5.6 [5.0; 6.0] mmol/l). During 3 months, glycated hemoglobin decreased from 7.5 [6.6; 8.5] to 5.7 [5.3; 5.9]%. In the early period following BPD, there was an increase in basal and postprandial GLP-1 levels associated with the peak IRI concentration. In the late period after BPD, the enhanced secretion of IRI and GLP-1 persisted, which was followed by a reduction in postprandial glucose levels in 4 of the 23 patients. T2DM remission does not depend on weight loss in the early period after BPD. In this period, the significant improvement of glucose metabolic parameters in patients with obesity and T2DM is associated with elevated GLP-1 levels. The altered incretin response is a stable effect of BPD and remains in its late period.

A meta-analysis of efficacy of Morus alba Linn. to improve blood glucose and lipid profile.

The previous studies have reported the Morus alba may improve blood glucose and lipid profile. The evidence from these studies is not consistent. This meta-analysis was to evaluate efficacy of products derived from M. alba on blood glucose and lipid levels. Literature was reviewed via international database (PubMed, PubMed Central, ScienceDirect, and SciSearch) and Thai databases. Thirteen RCTs with high quality, assessed by Jadad score, were included. M. alba expressed a significant reduction in postprandial glucose (PPG) at 30min (MD -1.04, 95% CI -1.36, -0.73), 60min (MD -0.87, 95% CI -1.27, -0.48) and 90min (MD -0.55, 95% CI -0.87, -0.22). The difference was not found in the levels of other glycaemic (FBS, HbA1C, or HOMA-IR) and lipidaemic (TC, TG, LDL, or HDL) markers. Serious adverse effects were found neither in the control nor in the group received M. alba. Products derived from M. alba can effectively contribute to the reduction in PPG levels, but large-scale RCTs would be informative.

A randomized study of raisins versus alternative snacks on glycemic control and other cardiovascular risk factors in patients with type 2 diabetes mellitus

Just as the type and duration of physical activity can have variable effects on the glucose levels and other cardiometabolic parameters among patients with type 2 diabetes mellitus (T2DM), so can the types of foods have variable effects as well. This 12-week randomized study of 51 study participants evaluated the impact of routine consumption of dark raisins versus alternative processed snacks on glucose levels and other cardiovascular risk factors among patients with type T2DM. In this study, compared to alternative processed snacks, those who consumed raisins had a significant 23% reduction in postprandial glucose levels (P = 0.024). Also compared to snacks, those who consumed raisins had a 19% reduction in fasting glucose and 0.12% reduction in hemoglobin A1c, although these latter findings did not achieve statistical significance. Regarding blood pressure, compared to alternative processed snacks, those who consumed raisins had a significant 8.7 mmHg reduction in systolic blood pressure (P = 0.035) (7.5% [P = 0.031]) but did not experience a significant reduction in diastolic blood pressure. Compared to alternative processed snacks, those who consumed raisins did not have a significant improvement in body weight, body mass index, waist circumference, fasting insulin, homeostatic model assessment of insulin resistance, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL), triglyceride, or non-HDL cholesterol levels. Overall, these data support raisins as a healthy alternative compare to processed snacks in patients with T2DM.

Postprandial glucose-lowering effects of fermented red ginseng in subjects with impaired fasting glucose or type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial.

BackgroundRed ginseng is prepared by steaming raw ginseng, a process believed to increase the pharmacological efficacy. Further bioconversion of red ginseng through fermentation is known to increase its intestinal absorption and bioactivity, and bioconversion diminishes the toxicity of red ginseng’s metabolite. This study was conducted to investigate the effects of daily supplementation with fermented red ginseng (FRG) on glycemic status in subjects with impaired fasting glucose or type 2 diabetes.MethodsThis study was a four-week long, randomized, double-blind, placebo-controlled trial. Forty-two subjects with impaired fasting glucose or type 2 diabetes were randomly allocated to two groups assigned to consume either the placebo or fermented red ginseng (FRG) three times per day for four weeks. Fasting and postprandial glucose profiles during meal tolerance tests were assessed before and after the intervention.ResultsFRG supplementation led to a significant reduction in postprandial glucose levels and led to an increase in postprandial insulin levels compared to the placebo group. There was a consistently significant improvement in the glucose area under the curve (AUC) in the FRG group. However, fasting glucose, insulin, and lipid profiles were not different from the placebo group.ConclusionDaily supplementation with FRG lowered postprandial glucose levels in subjects with impaired fasting glucose or type 2 diabetes.Trial registrationClinicalTrials.gov: NCT01826409

A Review of the Health Benefits of Raisins

There have been relatively few studies conducted on the health benefits of dried fruits; however, over the past few years there have been many advances regarding the health benefits of raisins. Williamson and Carughi (2012) recently reviewed the polyphenol content and health benefits of raisins. The review showed that raisins contain significant amounts of the flavonols quercetin and kaempferol and the phenolic acids caftaric and coutaric. Both quercetin and kaempferol are found in raisins as glycosides. Although the bioavailability of these compounds has not been studied in raisins, they have been shown to be well absorbed from other foods. These compounds may be responsible for some of the health benefits that have been reported with raisin consumption (Williamson and Carughi 2012). During the dehydration of grapes to raisins there is a significant loss of specific phenolic acids and polyphenols. However, total antioxidant capacity and total polyphenol contents remain relatively unchanged. Moreover, when equivalent amounts of grapes are fed either as fresh grapes, raisins, or wine (non-alcoholic) similar amounts of certain phenolic acid metabolites are detected in the urine. Thus, phenolic acids appear to be more bioavailable in raisins than in grapes and white wine (Murphy 2012). A webcast regarding the Emerging Health Benefits of Traditional Dried Fruit was presented on July 18, 2012 as a satellite session to the 2012 Institute of Food Technologists (IFT) annual meeting. This webcast was designed to review the latest research on the health benefits of raisins. The webcast included research studies regarding raisins and dental health by Allen Wong, D.D.S., Ed.D; heart disease and glycemic response by James Anderson, MD; satiety and energy intake by Barkha Patel, M.Sc.; and phytonutrient content by Rui Hai Liu, M.D., Ph.D. This supplement includes review papers from this webcast. Grape consumption, in the form of fresh grapes, raisins, and 100% grape juice, is associated with an overall increase in diet quality and nutrient intake. In “Improved Diet Quality and Increased Nutrient Intakes Associated with Grape Product Consumption by U.S. Children and Adults: National Health and Nutrition Examination Survey 2003–2008”, Debra Keast compared the diet quality of grape consumers (GC) with non-grape consumers (NGC). Compared to NGC, GC had higher intakes of total and whole fruit along with lower intakes of solid fat and added sugars. The grape consumers had higher intakes of several key nutrients including dietary fiber, vitamin A, vitamin C, calcium, and potassium. In “Raisins and Oral Health”, Allen Wong, D.D.S., Ed.D, discussed how current research shows some evidence that raisins may not contribute to dental caries, contrary to traditional thought. This paper reviews new findings with regards to raisins and the three conditions that are thought to contribute to the formation of dental caries; low oral pH, adherence of food to teeth, and biofilm (bacterial) behavior. The consumption of raisins has also been shown to improve blood glucose control and reduce risk for cardiovascular disease. In “Raisin Consumption by Humans: Effects On Glycemia and Insulinemia and Cardiovascular Risk Factors” James Anderson, M.D. reviews past research on the cardiovascular protective effects of raisins including their effects in reducing oxidized LDL (Barnes and others 2011) and reducing low-density lipoprotein (LDL) cholesterol (Puglisi and others 2008). The effect of the regular consumption of raisins on reduction of post-prandial glucose levels, HgbA1C, and blood pressure are also reviewed (Bays and others 2012 a, b) In “An After-School Snack of Raisins Lowers Cumulative Food Intake in Young Children” Barkha Patel, M.Sc. discusses how raisins as an after-school snack lower cumulative intake over the day compared to other snacks (potato chips, cookies). The researchers also discussed how the consumption of raisins before lunch can reduce calorie consumption at the subsequent meal. Researchers suggest that raisins as a snack may support appetite and weight control, thus reducing the risk for obesity (Patel and others 2011). In “Dietary Bioactive Compounds and Their Health Implications”, Rui Hai Liu, M.D., Ph.D, covered current research on phytochemicals in raisins and the prevention of chronic disease. Evidence suggests that health benefits of raisins may be attributed to the synergistic effects of phytochemicals present in whole foods.

Journal of Diabetes NEWS

<i>Journal of Diabetes</i> NEWS

Direct renin inhibitor aliskiren in women with menopausal metabolic syndrome and arterial hypertension

Aim. To study the effectiveness of a direct renin inhibitor, aliskiren, in patients with menopausal metabolic syndrome (MMS), and to assess aliskiren effects on blood pressure (BP), carbohydrate and lipid metabolism parameters, microalbuminuria, and arterial stiffness. Material and methods. The study included 23 women with MMS, to whom aliskiren monotherapy (150-300 mg/d) was administered. At baseline and in the end of the study, anthropometry, carbohydrate and lipid metabolism parameters assessment, 24-hour BP monitoring, and arterial stiffness assessment by volume sphygmography were performed. Results. By the end of the study, most parameters of circadian BP profile significantly decreased. Target levels of systolic and diastolic BP were achieved in 80 % of the patients. There was a significant reduction in postprandial glucose levels. According to the volume sphygmography results, a decrease in arterial stiffness was accompanied by a significant reduction in pulse wave velocity and augmentation index, with normalization of the former parameter. Conclusion. Aliskiren therapy demonstrated not only high antihypertensive effectiveness in MMS patients, but also a reduction in postprandial glucose levels and arterial stiffness.

The role of rapid-acting insulin analogues and inhaled insulin in type 2 diabetes mellitus

sBackground: The availability of rapid-acting insulin analogues and inhaled insulin gives clinicians additional treatmentoptions in the management of patients with diabetes mellitus (DM). Combining rapid-acting insulin analogues with basal insulin can more closely mimic physiologic insulin release to maximize glycemic control. Objective: The objective of this article was to discuss the role of rapid-acting insulin analogues and inhaled insulin inthe treatment of patients with type 2 DM. Methods: Materials for this article were obtained through an online search of MEDLINE/PubMed and Google(1996-2006) using the search terms bolus insulin, postprandial, rapid-acting insulin analogues, titration, hypoglycemia, glycemic control, inhaled insulin, and insulins lispro, aspart, and glulisine. Results: Glycosylated hemoglobin (A1C) levels and number of all hypoglycemic episodes were similar in patients withtype 2 DM taking either mealtime rapid-acting insulin analogues or regular human insulin (RHI). Rapid-acting insulins have been successfully used in basal-bolus regimens with a variety of long- and intermediate-acting insulins, as well as with oral hypoglycemic agents. Injectable rapid-acting insulin analogues markedly decreased postprandial glucose (PPG) levels compared with RHI. Better reduction in PPG levels may be key to achieving target A1C levels in some patients, but long-term outcome studies are needed to assess whether lowering PPG levels decreases cardiovascular risk in patients with type 2 DM. Inhaled insulin may be an option for patients who cannot inject insulin, but route of administration and dosing issues limit its use in many patients. The effect of inhaled insulin on PPG is unclear at this time. Conclusions: Although rapid-acting insulin analogues are effective in the management of patients with type 2 DM, the limited numbers of studies have yet to demonstrate that these agents have any significant long-term advantage compared with RHI. In addition, they cost more than RHI. Further studies are needed to compare the efficacy of the rapid-acting insulin analogues, to compare the different dosing regimens used with mealtime insulin administration, and to ascertain if the decrease in PPG levels seen with the use of rapid-acting insulin analogues translates into improved glycemic control and perhaps even a reduction in cardiovascular risk in patients with type 2 DM. (Insulin. 2007;2:61-67) Copyright 2007 Excerpta Medica, Inc.

Pioglitazone and reductions in post‐challenge glucose levels in patients with type 2 diabetes

Pioglitazone (PIO) has been shown to decrease insulin resistance in patients with type 2 diabetes, resulting in lowered blood glucose concentrations, lowered plasma insulin levels and lowered haemoglobin A1C (A1C) values. Postprandial glucose control has been recently recognized as an important target for reducing overall glycemic burden in patients with type 2 diabetes. Some authors assert that reductions in postprandial glucose levels may lead to a decrease in cardiovascular risk, one of the major complications associated with diabetes. Data were analysed from a 26-week PIO monotherapy study of 88 patients who underwent a 3-h oral glucose tolerance test (75 g dose) at baseline and last measurement. Change from baseline in area under the curve (AUC) values and hourly glucose concentrations were calculated and analysed at both time points for four medication groups: placebo group and PIO 15, 30 and 45 mg groups. Changes from baseline in fasting plasma glucose (FPG) and A1C also were reported. Glucose AUC was significantly (p < 0.05) different from baseline at 15, 30 and 45 mg doses of PIO. In addition, when compared to placebo, PIO (15, 30 and 45 mg) significantly decreased post-challenge blood glucose AUC (p < 0.05). The mean hourly blood glucose levels at last measurement for PIO 15, 30 and 45 mg all were significantly lower (p < 0.05) than placebo at all four time points. In addition, PIO significantly (p < 0.05) reduced FPG and A1C from baseline to last measurement in a dose-related fashion. PIO significantly reduced post-challenge glucose levels following an oral glucose challenge, leading to improvements in overall glycemic control. Postprandial glucose lowering is one of several metabolic effects of PIO in addition to decreasing insulin resistance and improving some lipids components. Whether these combined metabolic effects can lead to cardiovascular risk reductions may be confirmed by the pending results of cardiovascular outcomes studies with PIO.

Functional silencing of hepatic microsomal glucose-6-phosphatase gene expression in vivo by adenovirus-mediated delivery of short hairpin RNA

An expression cassette containing mouse U6 polymerase III promoter directing expression of short hairpin RNA (shRNA) targeting murine microsomal glucose-6-phosphatase (G6P) transcript was generated. This construct was packaged into an adenoviral (AdV) backbone and viral stocks generated. Mice injected intravenously with AdV-G6PshRNA exhibited a significant reduction in postprandial glucose levels and had significantly elevated steady-state hepatic glycogen stores. Target gene silencing was confirmed by measurements demonstrating a significant reduction in both hepatic G6P transcript level and phosphohydrolase activity. These findings provide evidence that AdV delivery of expressed shRNA can be a productive tool to explore gene function in vivo.