Treatment With an Oral Proteinase Inhibitor Slows Gastric Emptying and Acutely Reduces Glucose and Insulin Levels After a Liquid Meal in Type II Diabetic Patients

Schwartz, Joyce G.; Guan, Difu; Green, Gary M.; Phillips, William T.

doi:10.2337/diacare.17.4.255

Cited by 53 publications

(45 citation statements)

References 21 publications

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“…It is possible that SLD operates by a similar mechanism of action as CLA. SLD is a standardized potato extract containing 5% PPI II, which elicits a satiety response (19) and delays gastric emptying in humans (20). This is peculated to occur via the increased release of CCK, one of the most extensively studied peptides involved in the regulation of food intake (25).…”

Section: Discussionmentioning

confidence: 99%

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Anti-obesity and anti-diabetic effects of a standardized potato extract in ob/ob mice

Sung²,

Choung³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The potato (Solanum tuberosum) has been cultivated globally for food for millenia. Potato contains proteinase inhibitor II, which catalyzes the release of cholecystokinin (CCK), leading to delayed gastric emptying in humans. The present study investigated the anti-obesity effects of Slendesta™ Potato Extract (SLD), a standardized potato extract containing 5% proteinase inhibitor II, in the ob/ob obese mice. Three doses of SLD (50, 150 or 300 mg/kg) were orally administered to ob/ob mice once a day for 28 days, whereas control mice were administered distilled water. Four weeks after SLD treatment, the changes in body weight, food consumption, epididymal fat weight, serum chemistry, insulin, leptin and adiponectin contents, and fat histopathology were determined and compared with ob/ob mice treated with 750 mg/kg conjugate linoleic acid. As a result of SLD treatment in the obese mice, body weight, food consumption, epididymal fat, serum biochemistry, histomorphological changes of fat and pancreas were significantly and dose-dependently decreased compared with ob/ob control mice. These obesity and type 2 diabetes associated alterations were significantly inhibited after SLD treatment for 28 days. Thus, the present results indicate that SLD has potential as an alternative therapeutic agent for obesity.

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Section: Discussionmentioning

confidence: 99%

“…The potato tuber (Solanum tuberosum) is the source of potato proteinase inhibitor (PPI) II, which elicits a satiety response (19) and delays gastric emptying in humans (20). While several methods to isolate and purify PPI II have been developed for use in a laboratory setting, they are all laborious and expensive (21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Anti-obesity and anti-diabetic effects of a standardized potato extract in ob/ob mice

Sung²,

Choung³

et al. 2016

Experimental and Therapeutic Medicine

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“…The nutrient supply into the systemic circulation, which is predominantly regulated by the velocity of gastric emptying, has been demonstrated to be a major determinant of postprandial glucose and insulin concentrations (11,12,27). Notably, at least 35% of the variance in postprandial glucose levels can be explained by gastric emptying (11).…”

Section: Discussionmentioning

confidence: 99%

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

et al. 2005

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Glucagon-like peptide 1 (GLP-1) has been proposed to act as an incretin hormone due to its ability to enhance glucose-stimulated insulin secretion. Because GLP-1 also decelerates gastric emptying, it physiologically reduces rather than augments postprandial insulin secretory responses. Therefore, we aimed to antagonize the deceleration of gastric emptying by GLP-1 to study its effects on insulin secretion after a meal. Nine healthy male volunteers (age 25 ؎ 4 years, BMI 25.0 ؎ 4.9 kg/m 2 ) were studied with an infusion of GLP-1 (0.8 pmol ⅐ kg ؊1 ⅐ min ؊1 from ؊30 to 240 min) or placebo. On separate occasions, the prokinetic drugs metoclopramide (10 mg), domperidone (10 mg), cisapride (10 mg, all at ؊30 min per oral), or erythromycin (200 mg intravenously from ؊30 to ؊15 min) were administered in addition to GLP-1. A liquid test meal (50 g sucrose and 8% mixed amino acids in 400 ml) was administered at 0 min. Capillary and venous blood samples were drawn for the determination of glucose (glucose oxidase), insulin, C-peptide, GLP-1, glucagon, gastric inhibitory polypeptide (GIP), and pancreatic polypeptide (specific immunoassays). Gastric emptying was assessed by the phenol red dilution technique. Statistical analyses were performed using repeated-measures ANOVA and Duncan's post hoc test. GLP-1 significantly decelerated the velocity of gastric emptying (P < 0.001). This was completely counterbalanced by erythromycin, whereas the other prokinetic drugs used had no effect. Postprandial glucose concentrations were lowered by GLP-1 (P < 0.001 vs. placebo), but this effect was partially reversed by erythromycin (P < 0.05). Insulin secretory responses to the meal were lower during GLP-1 administration (P < 0.05 vs. placebo). However, when erythromycin was added to GLP-1, insulin concentrations were similar to those in placebo experiments. The suppression of meal-related increments in glucagon secretion by GLP-1 was reversed by erythromycin (P < 0.001). The time course of GIP secretion was delayed during GLP-1 administration (P < 0.05), but when erythromycin was added, the pattern was similar to placebo experiments. GLP-1 administration led to a reduction in pancreatic polypeptide plasma concentrations (P < 0.05). In contrast, pancreatic polypeptide levels were markedly increased by erythromycin (P < 0.001). Intravenous erythromycin counteracts the deceleration of gastric emptying caused by GLP-1, probably by interacting with the parasympathetic nervous system (pancreatic polypeptide responses). Despite augmented rises in insulin secretion, the glucose-lowering effect of GLP-1 is markedly reduced when the deceleration of gastric emptying is antagonized, illustrating the importance of this facet of the multiple antidiabetic actions of GLP-1. Diabetes 54: 2212-2218, 2005 I nsulin secretion after meal ingestion is stimulated not only by the rise in glycemia, but also by the secretion of peptide hormones ("incretins") from the gut (1,2). The postprandial enhancement of insulin secretion by gut-derived factors is called the ...

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“…Indeed, modi®cation of eating rate pharmacologically, 46 by diet 47 or by gastric restrictive surgery may be a feasible treatment of the metabolic syndrome by reducing the rate of glucose absorption and glucose-stimulated insulin release.…”

Section: Discussionmentioning

confidence: 99%

Metabolic correlates of eating behavior in severe obesity

et al. 2001

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BACKGROUND:The bene®t of spreading energy intake over many small meals (`nibbling') rather than few large ones (`gorging') for control of blood glucose, serum lipids and body fat accretion has been known for 60 y, but the mechanisms are poorly understood. Men exhibit more of a gorging eating pattern than women and are also more prone to the metabolic complications of obesity, as are women with a`male', central distribution of adipose tissue. We have shown correlations between central fat distribution, and other components of the metabolic`Syndrome X' and fatty in®ltration of the liver. Here we study relationships between eating rate and fat distribution and test the hypothesis that gorging might be associated with fatty liver. SUBJECTS AND METHODS:In 30 non-alcoholic, non-diabetic, severely obese women (body mass index, BMI 47 AE 1 kgam 2 ; mean AE s.e.m.) with a mean age of 36 AE 1 y and 16 men (BMI: 52 AE 3) age 38 AE 2 y, who were candidates for anti-obesity surgery, we measured eating rate using an eating monitor, and fat distribution by the waist ± hip circumference ratio (WHR). In addition in the 17 women and 11 men who had surgery, serum lipids were analyzed and routine liver biopsies were evaluated for steatosis by a pathologist blinded to the conditions of the study. RESULTS: Men ate signi®cantly faster than women (188 AE 28 vs 123 AE 9 gamin; P`0.01), and had more liver fat (score: 2.7 AE 03 vs 1.5 AE 0.3; P`0.01), with no statistically signi®cant sex differences in s-cholesterol or s-triglycerides. Eating rate correlated with WHR (r 0.46; P`0.01, n 46), liver fat (r 0.55; P`0.01), and s-triglycerides (r 0.42; P`0.05) adjusting for sex. Liver fat correlated with WHR (r 0.50; P`0.05), s-triglycerides (r 0.70; P`0.01) and s-cholesterol (r 0.50; P`0.05), while there were no signi®cant correlations with BMI or body weight. In multivariate analysis eating rate (32%), meal size (8%) and WHR (6%) contributed 46% of the variance in liver fat. CONCLUSION: We showed increased eating rates in severely obese men and women with central fat distribution. Furthermore, increased eating rates were associated with fatty liver and elevated serum lipids. Eating rate in severely obese women and men may be a determinant of the metabolic syndrome.

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Treatment With an Oral Proteinase Inhibitor Slows Gastric Emptying and Acutely Reduces Glucose and Insulin Levels After a Liquid Meal in Type II Diabetic Patients

Cited by 53 publications

References 21 publications

Anti-obesity and anti-diabetic effects of a standardized potato extract in ob/ob mice

Anti-obesity and anti-diabetic effects of a standardized potato extract in ob/ob mice

Erythromycin Antagonizes the Deceleration of Gastric Emptying by Glucagon-Like Peptide 1 and Unmasks Its Insulinotropic Effect in Healthy Subjects

Metabolic correlates of eating behavior in severe obesity

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