Increase In Postprandial Glucose Levels Research Articles

Temporal multiscale modeling of biochemical regulatory networks: Calcium-regulated hepatocyte lipid and glucose metabolism

Hepatocyte lipid and glucose metabolism is regulated not only by major hormones like insulin and glucagon but also by many other factors, including calcium ions. Recently, mitochondria-associated membrane (MAM) dysfunction combined with incorrect IP3-receptor regulation has been shown to result in abnormal calcium signaling in hepatocytes. This dysfunction could further lead to hepatic metabolism pathology. However, the exact contribution of MAM dysfunction, incorrect IP3-receptor regulation and insulin resistance to the calcium-insulin-glucagon interplay is not understood yet. In this work, we analyze the role of abnormal calcium signaling and insulin dysfunction in hepatocytes by proposing a model of hepatocyte metabolic regulatory network with a detailed focus on the model construction details besides the biological aspect. In this work, we analyze the role of abnormal calcium signaling and insulin dysfunction in hepatocytes by proposing a model of hepatocyte metabolic regulatory network. We focus on the model construction details, model validation, and predictions. We describe the dynamic regulation of signaling processes by sigmoid Hill function. In particular, we study the effect of both the Hill function slope and the distance between Hill function extremes on metabolic processes in hepatocytes as a model of nonspecific insulin dysfunction. We also address the significant time difference between characteristic time of glucose hepatic processing and a typical calcium oscillation period in hepatocytes. Our modeling results show that calcium signaling dysfunction results in an abnormal increase in postprandial glucose levels, an abnormal glucose decrease in fasting, and a decreased amount of stored glycogen. An insulin dysfunction of glucose phosphorylation, glucose dephosphorylation, and glycogen breakdown also cause a noticeable effect. We also get some insight into the so-called hepatic insulin resistance paradox, confirming the hypothesis regarding indirect insulin action on hepatocytes via dysfunctional adipocyte lipolysis.

Alpha-glucosidase and Alpha-amylase inhibitory activity by poly herbal extract with reference to positive control acarbose

It is well known that type 2 diabetes is an endocrine disease. Among glucose-lowering medications, α glucosidase which is a membrane bound enzyme at the epithelium of the small intestine that catalyses the cleavage of glucose from disaccharide are effective for delaying for glucose absorption. i.e., inhibitors delay the absorption of ingested carbohydrates, reducing the postprandial glucose. Pancreatic α-amylase is a key enzyme in the digestive system and catalyses the initial step in hydrolysis of starch to a mixture of smaller oligosaccharides consisting of maltose, maltotriose and a number of a-(l-6) and a-(1-4) oligoglucans. These are then acted on by alpha-glucosidases and further degraded to glucose which on absorbtion enters the blood-stream. Degradation of this dietary starch proceeds rapidly and leads to elevated PPHG (post-prandial hyperglycemia). It has been shown that activity of HPA (human pancreatic alpha-amylase) in the small intestine correlates to an increase in post-prandial glucose levels, the control of which is therefore an important aspect in treatment of type 2 diabetes. Pancreatic a-amylase inhibitors offer an effective strategy to lower the levels of post-prandial hyperglycemia via control of starch breakdown. By this study the Herbal extract demonstrated potent inhibitory activity for both the enzymes.

A pilot study on the effect of d-allulose on postprandial glucose levels in patients with type 2 diabetes mellitus during Ramadan fasting

BackgroundDuring Ramadan fasting, postprandial hyperglycemia is commonly observed after iftar (break of fast at sunset) meal. d-allulose is a rare sugar and is reported to have several health benefits, including the suppression of increase in postprandial glucose levels. This study investigates whether d-allulose (a C-3 epimer of d-fructose) improves the postprandial glucose in patients with type 2 diabetes mellitus (T2DM) during Ramadan.MethodsThis was a pilot, prospective single-arm study design that was conducted for 10 consecutive days; 5 days of control and 5 days of consumption. The primary outcome was postprandial peak glucose levels. During the consumption period, 8.5 g of d-allulose was consumed by the participants before iftar meal. Postprandial glucose was measured using a continuous glucose monitoring system.ResultsA total of 12 participants completed the study. Significant lower (p < 0.01) postprandial glucose values and the glucose incremental area under the curve (iAUC) were observed from 0 to 180 min during the consumption period compared to the control period. The consumption period demonstrated significantly higher percentages of time in which glucose values were found in the target range (p = 0.0032), and when the glucose levels above the target range were reduced (p = 0.0015).ConclusionsThe supplementation with d-allulose has the potential to improve postprandial hyperglycemia in patients with T2DM after iftar during Ramadan. Further studies are needed to confirm these findings.Trial registration ClinicalTrials.gov NCT05071950. Retrospectively registered, 8 October 2021.

The Glycemic Response to Infant Formulas: A Randomized Clinical Trial.

Background: Commercial infant formulas attempt to imitate human milk’s unique composition. However, lactose-free and milk protein-free formulas are often chosen due to medical reasons or personal preferences. The aim of this study was to determine the glycemic and insulinemic indices of a variety of infant formulas. Methods: We conducted a three-arm, randomized, double-blind, crossover study. Participants were 25–40-year-old healthy adults. Three commercial infant formulas (cow’s milk protein-based [“standard”], soy protein-based, and lactose-free) were randomly given to each participant. Glycemic and insulinemic responses were determined and compared between the three formulas. Results: Twenty subjects were enrolled (11 females/9 males, mean age 32.8 ± 2.9 years). No significant difference was found in the glycemic index between the three formulas (21.5, 29.1, and 21.5 for the standard, soy protein-based, and lactose-free formulas, respectively, p = 0.21). However, maximal glucose levels were significantly higher for the soy protein-based formula compared to both the standard and lactose-free formulas (111.5 compared to 101.8 and 105.8 mg/dL, respectively, p = 0.001). Conclusion: Cow’s milk protein-based, soy protein-based, and lactose-free formulas have a similar glycemic index. However, soy protein-based formula produced a significantly higher increase in postprandial glucose levels. The implication and biological significance of these results have yet to be determined.

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

Effect of high protein and fat diet on postprandial blood glucose levels in children and adolescents with type 1 diabetes in Cairo, Egypt

Background and aimsTo determine the effect of high protein and high fat meals on post prandial glycemia in patients with type 1 diabetes. MethodsThis study included 51 children and adolescents with type 1 diabetes who were following up at Diabetes, Endocrine and Metabolism Pediatric Unit (DEMPU), Abo Elrish Children’s hospital, Cairo University.Post prandial blood glucose levels were recorded and compared following three breakfast meals with varying protein and fat content (standard carbohydrate meal, high fat meal, and high protein meal) over a period of 5 hours on 3 consecutive days. ResultsHigh protein meal resulted in hyperglycemia with the peak level at 3.5 hours and continued for 5 hours post prandial while high fat meal caused early hyperglycemia reached the peak at 2 hours then declined towards 5 hours.Comparison of the three different breakfast meals revealed statistically significant difference regarding the postprandial glycemia at 30, 60, 90,120, 180, 210, 240, 270, 300 min. ConclusionMeals high in protein caused sustained increase in postprandial glucose levels over a period of 5 h. However, high fat meals caused early postprandial hyperglycemia. Protein and fat content of meals affect the timing and values of the peak blood glucose as well as the duration of postprandial hyperglycemia. Therefore, fat/protein unit should be taken in consideration while calculating the bolus insulin dose and anticipating the postprandial glucose response.

DNA methylation directs functional maturation of pancreatic β cells.

Pancreatic β cells secrete insulin in response to postprandial increases in glucose levels to prevent hyperglycemia and inhibit insulin secretion under fasting conditions to protect against hypoglycemia. β cells lack this functional capability at birth and acquire glucose-stimulated insulin secretion (GSIS) during neonatal life. Here, we have shown that during postnatal life, the de novo DNA methyltransferase DNMT3A initiates a metabolic program by repressing key genes, thereby enabling the coupling of insulin secretion to glucose levels. In a murine model, β cell-specific deletion of Dnmt3a prevented the metabolic switch, resulting in loss of GSIS. DNMT3A bound to the promoters of the genes encoding hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) - both of which regulate the metabolic switch - and knockdown of these two key DNMT3A targets restored the GSIS response in islets from animals with β cell-specific Dnmt3a deletion. Furthermore, DNA methylation-mediated repression of glucose-secretion decoupling genes to modulate GSIS was conserved in human β cells. Together, our results reveal a role for DNA methylation to direct the acquisition of pancreatic β cell function.

New insulins and insulin therapy

New insulins and insulin therapy

α-Glucosidase Inhibitiors from Seed Extract of Paeonia lactiflora

Alpha-glucosidase inhibitors are oral antihyperglycemic agents that act on alpha-glucosidase competitively, delaying intestinal carbohydrate absorption and lessening postprandial increases in glucose levels. In the search for new classes of α-glucosidase inhibitors extracted from natural resources, 420 different plant extracts were evaluated for their inhibitory effect on α-glucosidase, in vitro. Amongst the tested extracts, the seed extract of Paeonia lactiflora (Paeoniaceae) demonstrated a significant degree of inhibition on the enzyme, according to dose. Extensive bioassay-guided fractionation of the extract resulted in the isolation of six materials, luteolin (1), resveratrol (2), trans-e-viniferin (e), gnetin H (4), suffruticosol A (5) and suffruticosol B (6), that are active agents for α-glucosidase inhibition. Resveratrol (2) is a well-known naturally occurring hydroxystilbene, particularly abundant in wine and some related stilbene oligomers. Materials (3-6) exhibited relatively strong inhibition of α-glucosidase and their IC50 values were calculated as: 0.92mM (2), 3.15mM (3), 1.15 mM (4), 2.53mM (5) and 3.15mM (6). In contrast, the (IC50) value of the reference drug, acarbose, was estimated as 8.28mM in vitro.

Alpha glucosidase inhibition by stem extract of Tinospora cordifolia

Inhibitors of alpha glucosidase have potential use in the treatment of diabetes mellitus. The stem extract of Tinospora cordifolia was evaluated for inhibition of the enzyme. The extract was also found to inhibit the salivary and pancreatic amylase and therefore can effectively reduce an increase in postprandial glucose level. The crude ethyl acetate, dichloromethane (DCM), chloroform and hexane extracts of Tinospora cordifolia were studied. 15 mg of the DCM extract was most effective in that showed 100 % inhibition of the alpha glucosidase whereas salivary amylase was inhibited to the extent of 75 % and pancreatic amylase to 83 %. On giving a maltose load of 2mg / g along with 0.3 mg / g body weight of the DCM Tinospora stem extract a decrease was revealed in the hyperglycemic shoot up in normal and diabetic animals by 50 and 58 % respectively as compared to the controls. The extract was found to inhibit alpha glucosidase in a non-competitive manner.

Impaired Glucose Tolerance

Impaired glucose tolerance (IGT) is determined by measuring plasma glucose levels 2 hours after glucose loading in the oral glucose tolerance test. There is good evidence from epidemiologic and prospective trials [e.g. Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE)] linking IGT with the development of type 2 diabetes mellitus and cardiovascular disease (CVD). IGT is characterized by an increase in postprandial glucose levels, which is considered the earliest metabolic abnormality in type 2 diabetes mellitus. It is one of a series of risk factors for CVD (hypertension, high triglyceride levels, low high-density lipoprotein-cholesterol and central obesity), known as the metabolic syndrome. The different factors making up this syndrome are intimately related. An impaired lipid profile can contribute to insulin resistance, as IGT may play a pathogenic role on other cardiovascular risk factors. IGT is the first easily identifiable step in the pathophysiology of type 2 diabetes mellitus. It is associated with high risk for type 2 diabetes mellitus and subsequent vascular morbidity and mortality. It is currently unknown whether treating IGT will reduce the incidence of macrovascular complications, as studies addressing this issue have yet to be conducted. Therefore, the main reason to identify and treat IGT is to prevent or delay the onset of type 2 diabetes mellitus. It has been demonstrated that lifestyle intervention with diet and exercise can reduce the incidence of type 2 diabetes mellitus. Pharmacologic intervention with metformin and acarbose is also effective. Other drugs, such as those indicated to treat other parameters of the metabolic syndrome, may also be useful. We can now be assured that prevention or delay of onset of type 2 diabetes mellitus is possible in individuals with IGT, either by changes in lifestyle or by pharmacotherapy.

Alpha-Glucosidase inhibitory action of natural acylated anthocyanins. 1. Survey of natural pigments with potent inhibitory activity.

alpha-Glucosidase (AGH) inhibitory study by natural anthocyanin extracts was done. As the result of a free AGH assay system, 12 anthocyanin extracts were found to have a potent AGH inhibitory activity; in particular, Pharbitis nil (SOA) extract showed the strongest maltase inhibitory activity, with an IC(50) value of 0.35 mg/mL, as great as that of Ipomoea batatas (YGM) extract (IC(50) = 0.36 mg/mL). Interestingly, neither extract inhibited the sucrase activity at all. For the immobilized assay system, which may reflect the pharmacokinetics of AGH at the small intestine, SOA and YGM extracts gave more potent maltase inhibitory activities than those of the free AGH assay, with IC(50) values of 0.17 and 0.26 mg/mL, respectively. Both extracts also inhibited alpha-amylase action, indicating that anthocyanins would have a potential function to suppress the increase in postprandial glucose level from starch.

Laboratory tests in the elderly. What is abnormal?

Comparison of studies on the elderly is difficult. This study is one of the largest done on healthy, ambulatory persons aged 65 and up. Findings indicate that most laboratory values in elderly persons fall in the normal range. A significantly abnormal test result should raise the suspicion of underlying disease. A small percentage of patients show an abnormality on specific tests (ie, for glucose, calcium, serum lipids). Changes in a few test values are to be expected with aging: These include an increase in alkaline phosphatase, a decrease in serum phosphorus, a decrease in creatinine clearance without a concomitant rise in serum creatinine, and an increase in postprandial glucose level. Vitamin deficiencies and decrease in serum albumin are usually the result of chronic malnutrition rather than aging.