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G Weir

Publications and source records attributed to G Weir.

16 recordsLinked to original sources
PubMed1994

Ribozyme-mediated attenuation of pancreatic beta-cell glucokinase expression in transgenic mice results in impaired glucose-induced insulin secretion.

Phosphorylation of glucose to glucose 6-phosphate by glucokinase (GK; EC 2.7.1.2) serves as a glucose-sensing mechanism for regulating insulin secretion in beta cells. Recent findings of heterozygous GK gene mutations in patients with maturity-onset diabetes of the young (MODY), a form of type II (non-insulin-dependent) diabetes characterized by autosomal dominant inheritance, have raised the possibility that a decrease in beta-cell GK activity may impair the insulin secretory response of these cells to glucose. To generate an animal model for MODY we have expressed in transgenic mice a GK antisense RNA with a ribozyme element under control of the insulin promoter. Mice in two independent lineages had about 30% of the normal islet GK activity. Insulin release in response to glucose from in situ-perfused pancreas was impaired; however, the plasma glucose and insulin levels of the mice remained normal. These mice are likely to be predisposed to type II diabetes and may manifest increased susceptibility to genetic and environmental diabetogenic factors. They provide an animal model for studying the interaction of such factors with the reduced islet GK activity.

Animals↗
PubMed1992

[Val12] HRAS downregulates GLUT2 in beta cells of transgenic mice without affecting glucose homeostasis.

Glucose-induced insulin release from pancreatic beta cells depends on the beta-cell metabolism of glucose, which generates intracellular signals for secretion. The beta-cell glucose transporter isotype GLUT2 and the glucose phosphorylating enzyme glucokinase have both been implicated in coupling insulin secretion to extracellular glucose levels. Here we present evidence that a pronounced decrease in beta-cell GLUT2 has no immediate effect on glucose homeostasis. Analysis of transgenic mice overexpressing human [Val12]HRAS oncoprotein under control of the insulin promoter reveals a great reduction in plasma-membrane GLUT2 levels. These mice are nonetheless able to maintain normal fed and fasting plasma glucose and insulin levels for a period of several months. Insulin secretion studied in isolated islets and the perfused pancreas is characterized by a normal incremental response to increasing glucose concentrations. Glucose metabolism, as measured by glucose phosphorylation and oxidation in isolated islets, shows a normal dose dependence on extracellular glucose concentrations. These findings suggest that normal GLUT2 expression in beta cells is not essential for glucose sensing. The transgenic mice provide an experimental system for studying the role of glucose phosphorylation in regulation of insulin release in the absence of GLUT2.

Animals↗
PubMed1988

Oxidation of rat insulin II, but not I, leads to anomalous elution profiles upon HPLC analysis of insulin-related peptides.

Rat insulin II, unlike rat insulin I and other non-rodent insulins, contains a unique methionine residue at position B29. Reversed-phase HPLC allows for separation of the two rat insulins, with insulin I typically eluting faster than insulin II. An anomalous peak of insulin immunoreactive material was found eluting even faster than insulin I following acid extraction of rat insulin-producing cells. This early peak co-eluted with [Met-OB29]insulin II suggesting that during cell extraction and subsequent purification steps, rat insulin II is subject to selective oxidation at MetB29. Such oxidation of rat proinsulin II affords improved separation from rat proinsulin I compared to the native form.

Animals↗
PubMed1988

Community participation in the Mamre Community Health Project.

From the outset, community participation has been a working principle of the Mamre Community Health Project. The health planning approach was the predominant one used in Mamre. Attempts at improving community participation include the involvement of a steering committee elected by community members, the use of local people as interviewers and the feedback of results to the community in an accessible way. The process of negotiation of entry into the community was concluded. While consent and passive participation of the community were achieved, active participation remains a challenge for the future. Means of realistically evaluating community participation need to be developed.

Community Health Services↗
PubMed1984

Immunoblot identification of 13.5 kilodalton myelin basic protein in goldfish brain myelin.

Myelin isolated from goldfish brain shows a multilamellar structure with a major dense line and two intraperiod lines. Sodium dodecyl sulfate gel electrophoresis revealed that the protein profile of goldfish brain myelin is distinctly different from that of rat brain myelin. No protein migrating to the position of proteolipid protein or DM-20 was seen in goldfish myelin. Goldfish acclimated to 5 degrees, 15 degrees, and 30 degrees C showed no qualitative differences in myelin proteins. The 13.5 kD protein in goldfish brain myelin and brain homogenate was intensely immunostained with the antiserum to human basic protein by the immunoblot technique. In contrast, none of the proteins of goldfish myelin were immunostained with antiproteolipid protein serum; however, both proteolipid protein and DM-20 of rat brain myelin were immunostained. The significance of the synthesis of myelin proteins by astrocytes in the goldfish brain is discussed.

Adaptation, Physiological↗
PubMed1984

An in vivo analysis of pancreatic protein and insulin biosynthesis in a rat model for non-insulin-dependent diabetes.

The purpose of these experiments was to estimate insulin biosynthesis in vivo in a rat model for non-insulin-dependent diabetes. Insulin biosynthesis rates were determined in 4-wk-old animals that had been injected with 90 mg/kg of streptozotocin 2 d postpartum. Control and diabetic animals did not differ in body weight or fasting plasma glucose. Fed plasma glucose was significantly elevated (186 +/- 13 micrograms/dl vs. 139 +/- 7 mg/dl, P less than 0.05) and pancreatic insulin content was reduced (41 +/- 2 micrograms/g vs. 63 +/- 8 micrograms/g, P less than 0.05) in the diabetic rats. Insulin biosynthesis was estimated in vivo by measuring and comparing [3H]leucine incorporation into proinsulin with that into total pancreatic protein 45 min after injection. Insulin biosynthesis was 0.391 +/- 0.07% of pancreas protein synthesized in control rats and 0.188 +/- 0.015% (P less than 0.05) in diabetic rats. In animals of the same age, the fractional and absolute rate of pancreatic protein synthesis were determined. Total pancreatic protein synthesis was not reduced in streptozotocin treated animals (185.5 +/- 14.1%/d vs. 158.6 +/- 14.9%/d, NS) but was markedly reduced in control rats after a 48-h fast (to 70.8 +/- 5.5%/d, P less than 0.01). Because total pancreatic protein synthesis was not decreased in the diabetic rats, the decrease in the fraction of radiolabel incorporated into insulin seems to represent an absolute decrease in the rate of insulin biosynthesis in this animal model for diabetes. Through RNA blot hybridization with 32P-labeled cloned rat insulin complementary DNA, proinsulin messenger RNA (mRNA) was estimated as the rate of insulin biosynthesis in control and diabetic animals. There was a 61% reduction in proinsulin mRNA at 4 wk and an 85% reduction at 7 wk (P less than 0.001) in the diabetic animals. After streptozotocin injection in neonatal rats, there is marked beta-cell damage and hyperglycemia. Beta-cell regeneration occurs with return to normoglycemia, but with age hyperglycemia develops. The reduction in insulin synthesis and proinsulin mRNA seemed disproportionate with the more modest reduction in beta-cell number. The importance of these observations is that, in this animal model, diabetes is associated with a limited ability to regenerate beta-cell mass and to synthesize insulin. The relationship between the defect in glucose-stimulated insulin release and impaired insulin biosynthesis has yet to be determined.

Animals↗
PubMed1983

Egg-laying hormone: direct action on the ovotestis of Aplysia.

The bag cells are a group of neuroendocrine cells located in the abdominal ganglion of Aplysia californica. These cells induce egg laying in the animal through the release of neurohormone(s). Previous experiments established that an extract of bag cells releases eggs from isolated ovotestis fragments in a dose-dependent manner. (F. E. Dudek and S. S. Tobe, 1978, Gen. Comp. Endocrinol. 36, 618-627.) Experiments presented here were conducted to purify and identify the component(s) of bag cell extract with the egg-releasing activity. Bag cell extracts were fractionated by means of gel-filtration chromatography followed by cation-exchange chromatography. Column eluates were assayed for egg-release activity on isolated ovotestis fragments by the method of Dudek and Tobe (1978). Only one component purified from the crude extract had egg-releasing activity. This component was identified as egg-laying hormone (ELH) based on its purification characteristics, effects on neuronal activity, and migration on thin-layer chromatography. In dose-response studies egg release increased with the concentration of ELH and had a threshold of 8 X 10(-10) M or less. ELH had the same dose-response relationship in egg release assays when present in purified form or as a component of bag cell extract. These data show that ELH acts directly on the ovotestis and that ELH is the only component of bag cell extract with egg-release activity. Taken with the results of other studies (W. D. Branton, S. Arch, T. Smock, and E. Mayeri, 1978. Proc. Nat. Acad. Sci. USA 75, 5732-5736. B. S. Rothman, P. Brownell, and E. Mayeri, 1979. Soc. Neurosci. Abstr. 5, 260. E. Mayeri and B. S. Rothman, 1982.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗