Dopamine signalling facilitates motivated behaviours, and the D2 dopamine receptor (D2R) is important in mother-infant interactions. D2R antagonists disrupt maternal behaviour and, in isolated rat pups, reduce ultrasonic vocalizations (USVs) that promote maternal interaction. Here, we examined the effects of genetic D2R signalling deficiency on pup-dam interaction with Drd2 knockout (D2R KO) mice. Using heterozygous (HET) cross littermates, the effect of pup genotype on isolationinduced USVs was quantified. Independent of parental genotype, D2R-deficient pups emitted fewer USVs than wild type (WT) littermates in a gene dose-dependent manner. Using reciprocal D2R KO-WT crosses, we examined how parental genotype affects pup USVs. Heterozygous pups from D2R KO dams produced fewer USVs than HET pups from WT dams. Also, exposure to USV-emitting pups increased plasma prolactin levels in WT dams but not in D2R KO dams, and KO dams showed delayed pup retrieval and nest building. These findings indicate the importance of the interaction between pup and dam genotypes on behaviour and further support the role of D2R signalling in maternal care.
We hypothesized that individuals who have undergone gastric bypass have greater insulin sensitivity that obese subjects but less compared with lean. We measured free fatty acid (FFA) and glucose kinetics during a two-step, hyperinsulinemic euglycemic clamp in nondiabetic subjects who were 38 Ϯ 5 mo post-gastric bypass surgery (GB; n ϭ 15), in lean subjects (L; n ϭ 15), and in obese subjects (O; n ϭ 16). Fasting FFAa were not significantly different between the three study groups but during both doses of insulin were significantly higher in O than in either GB or L. The effective insulin concentration resulting in half-maximal suppression of FFA was similar in L and GB and significantly less in both groups compared with O. Glucose infusion rates during low-dose insulin were not significantly different in GB compared with either L or O. During high-dose insulin, glucose infusion rates were significantly greater in GB than in O but less than in L. Endogenous glucose production in GB was significantly lower than O only during low dose of insulin. We conclude that gastric bypass is associated with improvements in adipose tissue insulin sensitivity to levels similar to lean, healthy persons and also with improvements in the response of glucose metabolism to insulin. These changes may be due to preferential reduction in visceral fat and decreased FFA availability. However, some differences in insulin sensitivity in GB remain compared with L. Residual insulin resistance may be related to excess total body fat or abnormal lipolysis and requires further study. insulin sensitivity; glucose; body composition; obesity OBESITY IS FREQUENTLY ACCOMPANIED by insulin resistance (5). Elevated circulating free fatty acid (FFA) concentrations, due to increased adipose tissue lipolysis, are thought to mediate insulin resistance in both obesity and type 2 diabetes (4). Weight loss via a hypocaloric diet has been shown to reduce lipolysis in obese individuals (14). However, although gastric bypass surgery has been shown to improve insulin action on glucose metabolism, relatively little is known about the effect of gastric bypass surgery on the insulin sensitivity of adipose tissue.We measured FFA kinetics during a two-step hyperinsulinemic euglycemic clamp in nondiabetic individuals who had undergone gastric bypass surgery and in nondiabetic lean and obese subjects. We hypothesized that gastric bypass subjects have greater insulin sensitivity with respect to lipolysis compared with obese subjects but less than lean subjects. We also hypothesized that gastric bypass subjects would have greater insulin sensitivity with respect to glucose kinetics than obese subjects but less than lean subjects and that there would be a relationship between adipose tissue insulin sensitivity and the sensitivity of glucose metabolism to insulin.Research design and methods. The Mayo Institutional Review Board approved the study, and subjects gave informed consent. The Mayo Clinical Research Unit (CRU) was used for this study. Three groups of nondiabetic sub...
ObjectiveTo develop and validate a phenotyping algorithm for the identification of patients with type 1 and type 2 diabetes mellitus (DM) preoperatively using routinely available clinical data from electronic health records.Patients and MethodsWe used first-order logic rules (if-then-else rules) to imply the presence or absence of DM types 1 and 2. The “if” clause of each rule is a conjunction of logical and, or predicates that provides evidence toward or against the presence of DM. The rule includes International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes, outpatient prescription information, laboratory values, and positive annotation of DM in patients’ clinical notes. This study was conducted from March 2, 2015, through February 10, 2016. The performance of our rule-based approach and similar approaches proposed by other institutions was evaluated with a reference standard created by an expert reviewer and implemented for routine clinical care at an academic medical center.ResultsA total of 4208 surgical patients (mean age, 52 years; males, 48%) were analyzed to develop the phenotyping algorithm. Expert review identified 685 patients (16.28% of the full cohort) as having DM. Our proposed method identified 684 patients (16.25%) as having DM. The algorithm performed well—99.70% sensitivity, 99.97% specificity—and compared favorably with previous approaches.ConclusionAmong patients undergoing surgery, determination of DM can be made with high accuracy using simple, computationally efficient rules. Knowledge of patients’ DM status before surgery may alter physicians’ care plan and reduce postsurgical complications. Nevertheless, future efforts are necessary to determine the effect of first-order logic rules on clinical processes and patient outcomes.
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