Entero-pancreatic hormone secretion, gastric emptying and glucose absorption after frequently sampled meal tests

Context Entero-pancreatic hormone secretion has been reported during the pre-absorptive cephalic and gastric meal phases, but never with a blood sampling frequency providing a temporal resolution that allows close scrutiny and correlations with gastric emptying and glucose-absorption. Objective We hypothesized that entero-pancreatic hormone secretion after nutrient ingestion would be rapid and correlate with gastric emptying and glucose absorption. Design and setting Two visits in a clinical research facility. Participants Ten healthy young men. Interventions A 75g glucose drink (OG) and a liquid mixed meal (LMM) were ingested (t 0-2 min) on separate days. Acetaminophen and 3-O-methyl-D-glucopyranose (3-OMG) were added to the drinks to evaluate gastric emptying and glucose absorption, respectively. Arterialized venous blood was sampled (t -30,-20,-18,-16,-14,-12,-10,-8,-6,-4,-2, 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 30 min). Main outcome measures Plasma glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), gastrin, cholecystokinin (CCK), glucagon, pancreatic polypeptide (PP), 3-OMG and glucose. Serum insulin, C-peptide and acetaminophen. Results Acetaminophen increased 8min after OG(p<0.001) and LMM(p<0.05). 3-OMG; 8min after LMM(p<0.0001), 10min after OG(p=0.04). PP; 4min after LMM(p<0.03). Gastrin; 6min after LMM(p<0.003) and OG(p<0.003). CCK; 6min after LMM(p=0.0001). GIP; 8min after OG(p<0.05) and LMM(p<0.03). Glucose; 8min after OG(p<0.001), 12min after LMM(p<0.02). GLP-1; 12min after OG(p<0.01), 10min after LMM (p<0.01).. Insulin; 12min after LMM(p=0.02) and OG(p=0.002). C-peptide; 12min after OG(p=0.002) and LMM(p=0.04). Conclusions Early postprandial hormone responses show characteristic differences with regards to timing and amplitude, but also great individual differences. This should be considered when interpreting mean responses and designing study protocols. ClinicalTrials.gov number NCT03543423.

NANOPARTICLE INSULIN DRUG DELIVERY-APPLICATIONS AND NEW ASPECTS

Diabetes mellitus is a chronic metabolic disorder caused via the deficiency of pancreatic hormone insulin (Type1 diabetes mellitus) or due to the resistance of cells to insulin secreted by using the body (Type 2 diabetes mellitus). It is a rapidly growing serious situation that inspires a lot of global concern. Exogenous insulin administration is many times used therapy for Type 1 Diabetes Mellitus and gestational diabetes. The traditional subcutaneous insulin injections cause a lot of suffering to the affected person, exceptionally due to pain and secondarily due to dose sensitivity and in additional complications. Hence alternate delivery systems are an area of recreation for medical professionals and a convenient alternative system will be a boon to the patients. As an end result of the technological advances, various invasive and non-invasive delivery systems have been brought in the previous years. Nanotechnology, particle-mediated delivery, pulmonary delivery, buccal spray, etc. are the most current advances.

Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors

Dopamine (DA) and norepinephrine (NE) are catecholamines primarily studied in the central nervous system that also act in the pancreas as peripheral regulators of metabolism. Pancreatic catecholamine signaling has also been increasingly implicated as a mechanism responsible for the metabolic disturbances produced by antipsychotic drugs (APDs). Critically, however, the mechanisms by which catecholamines modulate pancreatic hormone release are not completely understood. We show that human and mouse pancreatic α- and β-cells express the catecholamine biosynthetic and signaling machinery, and that α-cells synthesize DA de novo. This locally-produced pancreatic DA signals via both α- and β-cell adrenergic and dopaminergic receptors with different affinities to regulate glucagon and insulin release. Significantly, we show DA functions as a biased agonist at α2A-adrenergic receptors, preferentially signaling via the canonical G protein-mediated pathway. Our findings highlight the interplay between DA and NE signaling as a novel form of regulation to modulate pancreatic hormone release. Lastly, pharmacological blockade of DA D2-like receptors in human islets with APDs significantly raises insulin and glucagon release. This offers a new mechanism where APDs act directly on islet α- and β-cell targets to produce metabolic disturbances.