Effect of delayed luminal carbodhydrate uptake via α-glucosidase inhibition on plasma glycemic parameters and lipid profiles in adult wistar fatty rats

Abstract

To determine the effects of delayed luminal glucose uptake on plasma glycemic and lipid profiles, groups of adult male lean and obese+NIDDM Wistar Fatty Rats (n=8 rats/ group) were fed nutritionally complete diets where the carbohydrate was provided as cooked cornstarch (CS), sucrose (SU), or the SU diet containing an admixture of the luminal α-glucosidase inhibitor compound acarbose (ACB, 150mg/kg diet) from 22 to 30weeks of age. Measures of body weight, caloric intake, fasting Insulin to glucose (I: G) ratios, and plasma cholesterol (CHOL), triglyceride (TG) and Alpha (LDL) and Beta (HDL) Lipoprotein concentrations were determined after 8weeks of the dietary regimen. Food intake and weight gain of the obese+NIDDM phenotype was greater than the lean phenotype, increased with the SU diet. The weight gains of lean and obese+NIDDM rats fed the SU+ACB diet were similar to rats of the same phenotype fed the ST diet. Fasting I:G ratios were elevated in Obese+NIDDM and were similar to those of ST fed rats fed the ACB diet. Plasma CHOL and TG were greater on obese+NIDDM rats of both sexes, and ACB was associated with modest decreases in CHOL concentrations in both lean and obese+NIDDM rats. No adverse side effects of the ACB were observed in either phenotype. These results indicate that luminal inhibition of carbohydrate digestion via α-glucoside inhibition was associated with improvements in I:G ratios and in plasma lipid profiles that were similar to those observed with the complex CHO ST diet and may be a safe and useful adjunct in the treatment of NIDDM and other carbohydrate intolerant states.

Effect of dietary carbohydrate type, biological sex and phenotype on glycemic responses in wistar fatty rats

“…When 22weeks of age, the diet was changed thereafter to isoenergetic semisynthetic diets consisting of (w/w) 54% carbohydrate as cooked cornstarch (CS) or sucrose (SUC), 16 % mixed fats (equal parts lard, corn oil, beef tallow, and coconut oil), 20% protein (as equal parts lactalbumin and casein), 4% essential vitamins and minerals and 5% cellulose fiber, plus continued free access to house water. 14 Animals were weighed weekly and measures of 24-hour food intakes recorded for estimation of feed efficiency ratios after 4 and 8weeks on the experimental diet. Measures of intraperitoneal glucose tolerance (glucose, 250mg/100g BW, in a 50% w/v sterile solution) were obtained at 30weeks of age after 8 weeks on the experimental diet.…”

“…The luminal absorption of monosaccharides once generated occurs rapidly without hormonal actions, while most peripheral tissues including skeletal muscle and adipose tissue are dependent on insulin actions for glucose uptake to occur, and in the presence of insulin resistance, delays the rate of glucose uptake in peripheral tissues. [12][13][14] The administration of a glucose tolerance test following a standardized dosage of glucose is among the most common laboratory assays to assess the status of glucose disposal and insulin resistance in peripheral tissues. 16 The slope of the glucose curve observed first 30-45 minutes following the administration of the glucose load corresponds to the rate of intestinal luminal glucose uptake following an orally administered glucose challenge, while the first 30minutes following an intraperitoneally administered dose of glucose reflects the systemic uptake from abdominal tissues, and may attain greater plasma concentrations than orally administered glucose due to the more rapid delivery to absorptive surfaces, in addition to a greater surface are of absorptive tissues.…”

Does Carbohydrate and Insulin Resistance of Obesity Contribute to the Senescence of Brain Atrophy in Aging? Here is What the Lab Rats May Be Telling Us about Carbohydrates

“…The luminal brush border enzymes of the upper small intestine play a critical role in the glycemic index of ingested carbohydrate sources, particularly those residing in the duodenum where the ingested carbohydrates make their first contact with luminal absorbance mechanisms before entry into the circulation for uptake into peripheral tissues [1][2][3]. The more rapid entry of the acid chyme into the duodenum in the obese phenotype enables more carbohydrate residues from more frequent meals to make their appearance for neutralization and immediate digestion and absorption, thereby eliciting a greater and more prolonged magnitude of insulinogenic response than occurs in their lean littermates, where the ingestion and gastrointestinal functions occur along a more graded time frame, even in the presence of a sucrose-rich diet and where metabolic regulation mechanisms remains operative.…”

“…The luminal absorption of dietary carbohydrate occurs with virtually 100% efficiency in the upper segments of the small intestine and occurs more rapidly with the digestion of high glycemic index simple carbohydrate sources such as sucrose vs lower glycemic index complex carbohydrate sources including cornstarch [1][2][3][4][5]. The brush border extensions lining the absorptive lumen of the small intestine are normally populated with a healthy abundance of sucrase and glucosidase enzymes, which have the enzymatic capacity to degrade disaccharides and complex carbohydrate polymers into absorbable monosaccharide moieties often within minutes of their presentation as…”

A Brief Review of Incretin Mimetics Intended for the Management of Diabetes and Associated Comorbidities

“…The American Diabetes Association's guidance encourages the adoption of a patient-centered strategy to direct further therapy, considering factors like cost, side effects, weight fluctuations, hypoglycemia risk, and efficacy with additional medication. Add-on therapy for metformin includes thiazolidinediones, dipeptidyl peptidase-4 inhibitors, insulin, sodium-glucose co-transporter two inhibitors, glucagon-like peptide-1 receptor agonists, luminal glucosidase inhibitors, diet, and sulfonylureas [6,10,11].…”