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At least 829 records · Page 46Linked to original sources
PubMed2003

Inflammation in the prediabetic state is related to increased insulin resistance rather than decreased insulin secretion.

BACKGROUND: Elevated levels of proinflammatory proteins are predictive of both cardiovascular (CV) disease and type 2 diabetes. Previously, atherogenic changes in traditional CV risk factors in the prediabetic state were mainly seen in insulin-resistant subjects rather than in those with a predominant defect in insulin secretion. METHODS AND RESULTS: We studied in prediabetic individuals from the Insulin Resistance Atherosclerosis Study (IRAS) the relation of C-reactive protein (CRP), plasminogen activator inhibitor (PAI)-1, and fibrinogen to defects in insulin sensitivity (SI) and first-phase insulin secretion, respectively, as assessed using a frequently sampled intravenous glucose tolerance test. One hundred forty-eight of 906 (16.3%) nondiabetic individuals developed diabetes after a mean follow-up of 5.2 years. Prediabetic individuals who were insulin resistant had higher levels of PAI-1 (mean [95% CI], 25.83 ng/mL [22.42 to 29.77] versus 16.31 ng/mL [12.56 to 21.18]; P=0.003) and CRP (mean [95% CI], 2.88 mg/L [2.33 to 3.56] versus 1.68 mg/L [1.13 to 2.49]; P=0.018) than insulin-sensitive individuals, but individuals with decreased acute insulin response tended to have lower rather than higher levels of inflammatory proteins compared with those with high insulin secretion. Prediabetic subjects who were predominantly insulin resistant had higher levels of inflammatory proteins compared with both prediabetic subjects with decreased insulin secretion as well as nonconverters. By contrast, prediabetic subjects with a predominant defect in first-phase insulin secretion had levels of inflammatory proteins indistinguishable from those in nonconverters. CONCLUSIONS: We have shown an increased proinflammatory state in prediabetic individuals who are predominantly insulin resistant but not in those with a primary defect in beta-cell function. These results provide additional evidence that prediabetic subjects may be at an increased risk of heart disease, and this risk seems to be restricted to subjects with high insulin resistance.

Adipose Tissue↗
PubMed1984

Effect of protein depletion on the VLDL triacylglycerol secretion and apoprotein synthesis by the perfused liver from pregnant rats.

The effect of protein depletion in the pregnant rat on the polyunsaturated fatty acid incorporation into very low density lipoproteins (VLDL) has been investigated. The apoprotein pattern of these particles was determined. In in vivo experiments the amounts of serum and liver triacylglycerol were determined. VLDL were isolated and their apo C concentration calculated. In in vitro experiments the radioactivity of [3H]leucine incorporated into VLDL apoproteins was measured. The results show that protein depletion during pregnancy promotes a drastic increase in serum and liver triacylglycerol. The VLDL isolated from these animals show an increase in the triacylglycerol/protein ratio and a decrease in their content of apo C. Meanwhile, a significant reduction in the [3H]leucine incorporation into apo C peptides by the perfused liver of protein depleted rats was detected. On the other hand, protein deprivation did not affect labeled linoleic and arachidonic acid incorporation into triacylglycerol of the newly secreted VLDL. Taking these results together, let us deduce that a defective VLDL is secreted by the liver of the protein depleted pregnant rats. The abnormal composition of these particles may influence its normal metabolism through their effects on lipoprotein lipase and this fact could affect the normal supply of polyunsaturated fatty acids to the fetus.

Animals↗
PubMed2001

Beta cell failure: causes and consequences.

In recent years a great deal of discussion has focused on the relative roles of insulin resistance and beta-cell dysfunction in the pathogenesis of type 2 diabetes. When considering their relative importance it is critical that the two variables are considered in concert. Alterations in insulin secretion are present in patients with type 2 diabetes and can be demonstrated in high risk individuals well before diagnosis. Loss of the early phase of insulin secretion can be demonstrated following oral or intravenous glucose administration. The relationship of early insulin secretion to insulin sensitivity in normal individuals is represented by a hyperbolic curve in keeping with the existence of a feedback loop. Deviations from standardised curves demonstrate defects in both insulin secretion and sensitivity in individuals who are at risk of developing diabetes. The reduction in the early phase insulin response results in impaired suppression of hepatic glucose production. Glucose output by the liver is not inversely proportionate to glucose influx, resulting in postprandial hyperglycaemia. Therapeutic approaches must address defects in both the early insulin response and insulin sensitivity. New oral agents that stimulate early insulin secretion and rapid-acting insulin analogues are targeting this early insulin secretion defect.

Diabetes Mellitus, Type 2↗
PubMed1996

Defective protein kinase C alpha leads to impaired secretion of soluble beta-amyloid precursor protein from Alzheimer's disease fibroblasts.

The present study shows that cultured fibroblasts from sporadic AD patients present: a) reduced (-30%) cytosolic protein kinase C (PKC) activity; b) increased KD of phorbol ester binding (+94%) in cytosolic fractions; c) reduced (-30%) soluble protein kinase C alpha immunoreactivity; d) lower (-27.5%) basal soluble APP secretion and e) reduced soluble APP secretion in response to low phorbol ester concentrations (over threefold difference using 9 nM phorbol-12,13-dibutyrate-PdBu). Since the PKC-stimulated secretion of APP leads to the cleavage of the precursor within the amyloidogenic beta-A4 fragment, the reduced PKC activity in AD patients may lead to accumulation of potentially amyloidogenic or toxic APP fragments. A defect in the secretion of soluble amyloid beta-protein precursor is indeed suggested by literature data on familial AD fibroblasts as well as by the reported results.

Alzheimer Disease↗
PubMed1996

[Non-insulin-dependent diabetes: from physiopathology to treatment].

Non-insulin-dependent (or type 2) diabetes mellitus is a common, underdiagnosed and growing disease in our society. It is responsible for increased morbidity and mortality and represents an important public health problem. This polygenic disease is often expressed late in life and its evolution is accelerated by environmental factors leading to obesity. It combines defects in both insulin secretion and insulin action, and such defects are present in various proportions according to the type of patient and the stage of the disease. Diet and physical activity recommendations are the basis of the treatment. Current pharmacological approaches aim at improving insulin secretion and/or insulin cellular action. After secondary failure to oral drugs, insulin therapy should be initiated, the patient becoming "insulin-requiring". A synergy should be searched in the combination of various therapeutic modalities in order to improve the glycaemic control.

Combined Modality Therapy↗
PubMed2003

Diazoxide attenuates glucose-induced defects in first-phase insulin release and pulsatile insulin secretion in human islets.

Humans with type-2 diabetes mellitus (TTDM) have hyperglycemia ( approximately 11 mM) and impaired glucose-mediated insulin secretion characterized by impaired first-phase insulin release (FPIR) and pulsatile insulin release. Culture of islets from nondiabetic humans in very high glucose concentrations ( approximately 20-30 mM) for 96 h causes impaired FPIR. We sought to determine 1). whether human islets cultured at a glucose concentration of approximately 11 mM (comparable to TTDM) recapitulates impaired insulin secretion in TTDM, specifically impaired FPIR and insulin pulse mass with an increased proinsulin/insulin (PI/I) secretion ratio; and 2). whether these changes can be attenuated by addition of diazoxide to islets cultured with 11 mM glucose. Islets cultured with 11 mM glucose for 96 h had 75% depleted insulin stores (P < 0.05), decreased FPIR and insulin pulse mass (P < 0.05), and an approximately 3-fold increase in the ratio of PI/I islet content and in secretion ratio (P < 0.05). Addition of diazoxide to islets cultured with 11 mM glucose decreased insulin secretion during static incubation, leading to relative preservation of insulin stores and enhanced insulin secretion during subsequent perifusion; FPIR increased by 162% (P < 0.05) and insulin pulse mass by 150% (P < 0.05) vs. no diazoxide. The mean islet PI/I content and islet PI/I secretion ratio were also decreased by approximately 70% (P < 0.05) by prior addition of diazoxide to islets during culture with 11 mM glucose. FPIR and insulin pulse mass were related to islet insulin stores (P < 0.001 for FPIR and P < 0.001 for pulse amplitude). In conclusion, the pattern of defects of insulin secretion present in TTDM (impaired FPIR and pulsatile insulin secretion, increased PI/I ratio) can be recapitulated in human islets cultured with 11 mM glucose for 96 h. These defects can be at least partially offset by concurrent inhibition of insulin secretion by diazoxide, which also preserves insulin stores. Defective insulin secretion in TTDM may be, at least in part, due to depletion of available insulin stores secondary to chronic increased demand (insulin resistance and hyperglycemia) in the setting of a decreased beta-cell mass.

Cells, Cultured↗
PubMed1999

The relation of proinsulin and insulin to insulin sensitivity and acute insulin response in subjects with newly diagnosed type II diabetes: the Insulin Resistance Atherosclerosis Study.

AIMS/HYPOTHESIS: Proinsulin concentrations are increased relative to insulin concentrations in subjects with Type II (non-insulin-dependent) diabetes mellitus. This could be secondary to hyperglycaemia or insulin resistance or due to a defect in insulin secretion. METHODS: We investigated the association between fasting insulin, intact proinsulin and the intact proinsulin: insulin ratio with insulin sensitivity, estimated by a frequently sampled intravenous glucose tolerance test and the minimal model and with acute insulin response (AIR) in 182 newly diagnosed Type II diabetic subjects aged 40 to 69 years. None of the subjects was receiving hypoglycaemic medication. RESULTS: Insulin sensitivity correlated inversely with fasting insulin (r(s) = -0.42) and intact proinsulin (r(s) = -0.32) (p < 0.001). The intact proinsulin:insulin ratio was not correlated with insulin sensitivity. AIR correlated positively with intact proinsulin (r(s) = 0.23) and inversely with the intact proinsulin:insulin ratio (r(s) = -0.29, p < 0.001). Fasting glucose correlated positively with intact proinsulin (r(s) = 0.34) and the intact proinsulin:insulin ratio (r(s) = 0.24, p < 0. 001). The intact proinsulin:insulin ratio increased by decreasing AIR (quartiles of AIR from high to low: 7.8, 8.2, 9.7 and 12.1 %, p < 0.001). This association was independent of age, sex, ethnicity, body mass index, fasting glucose, and insulin sensitivity. CONCLUSION/INTERPRETATION: Insulin resistance (low insulin sensitivity) was not related to the intact proinsulin:insulin ratio in subjects with Type II diabetes. In contrast, both low AIR and high fasting glucose concentrations were associated with a disproportionate increase in proinsulin concentration. These results suggest that increased intact proinsulin:insulin ratio is a marker of a defect in insulin secretion in Type II diabetic subjects.

Adult↗
PubMed2006

Beta-cell deficit due to increased apoptosis in the human islet amyloid polypeptide transgenic (HIP) rat recapitulates the metabolic defects present in type 2 diabetes.

Type 2 diabetes is characterized by defects in insulin secretion and action and is preceded by impaired fasting glucose (IFG). The islet anatomy in IFG and type 2 diabetes reveals an approximately 50 and 65% deficit in beta-cell mass, with increased beta-cell apoptosis and islet amyloid derived from islet amyloid polypeptide (IAPP). Defects in insulin action include both hepatic and extrahepatic insulin resistance. The relationship between changes in beta-cell mass, beta-cell function, and insulin action leading to type 2 diabetes are unresolved, in part because it is not possible to measure beta-cell mass in vivo, and most available animal models do not recapitulate the islet pathology in type 2 diabetes. We evaluated the HIP rat, a human IAPP transgenic rat model that develops islet pathology comparable to humans with type 2 diabetes, at age 2 months (nondiabetic), 5 months (with IFG), and 10 months (with diabetes) to prospectively examine the relationship between changes in islet morphology versus insulin secretion and action. We report that increased beta-cell apoptosis and impaired first-phase insulin secretion precede the development of IFG, which coincides with an approximately 50% defect in beta-cell mass and onset of hepatic insulin resistance. Diabetes was characterized by approximately 70% deficit in beta-cell mass, progressive hepatic and extrahepatic insulin resistance, and hyperglucagonemia. We conclude that IAPP-induced beta-cell apoptosis causes defects in insulin secretion and beta-cell mass that lead first to hepatic insulin resistance and IFG and then to extrahepatic insulin resistance, hyperglucagonemia, and diabetes. We conclude that a specific beta-cell defect can recapitulate the metabolic phenotype of type 2 diabetes and note that insulin resistance in type 2 diabetes may at least in part be secondary to beta-cell failure.

Amyloid↗
PubMed1993

Suppression by HIV of IL-1 and IL-6 secretion in accessory cells: AC function defect partially corrected with exogenous IL-1 and IL-6.

To determine the effect of HIV infection on the accessory cell function of monocytes we measured the ability of HIV-infected monocytes to restore PHA-induced and soluble anti-CD3-induced T cell blastogenesis. These T cells were highly purified and depleted of monocytes (< 0.5%) and activated T cells. Monocytes were isolated using gelatin-fibronectin-coated flasks (< 1% T cells) and after 4 days in culture with granulocyte/macrophage-colony stimulating factor, they were infected with HIV. Accessory cell (AC) function was tested 2 and 7 days later, employing autologous cryopreserved T lymphocytes. Monocytes infected with HIV for 2 days lacked the ability to permit phytohemagglutinin (PHA) and anti-CD3-induced T cell blastogenesis. Noninfected monocytes restored the proliferative response of purified T cells. Interleukin 1 (IL-1) and interleukin 6 (IL-6) levels in culture supernatants were low when compared to cultures with noninfected AC. Preincubation of monocytes with human anti-HIV neutralizing antibodies did not restore either of the responses. AC treated with heat-inactivated HIV had normal accessory cell function. The addition of IL-1 and/or IL-6 partially restored the AC function for PHA stimulation, but not for anti-CD3 stimulation. We conclude that HIV infection of monocytes suppressed their accessory cell function in the T cell blastogenesis assay. The response was partially restored with IL-1 and/or IL-6, suggesting that HIV infection down-regulated the monocyte production of both cytokines.

Antigen-Presenting Cells↗
PubMed1995

Defective clonidine-induced growth hormone secretion and normal thyroid and adrenal functions in prepubertal children with chronic renal insufficiency (CRF).

We evaluated clonidine-induced growth hormone (GH) secretion, insulin-like factor-I (IGF-I), free thyroxine (FT4), and thyroid stimulating hormone (TSH) concentrations, basal (8-h) as well as adrenocorticotrophic hormone (ACTH) provoked cortisol secretion in 14 prepubertal children suffering from chronic renal failure (CRF) with impaired statural growth [growth velocity (GV) = 3.7 +/- 0.3 cm/year] and compared these values with those of 10 normal age matched children with normal variant short stature (NVSS) (GV = 4.6 +/- 0.4 cm/year). The body mass indices and the bone age delay did not differ between the two groups (14.8 +/- 0.7 kg/m2 and 1.5 +/- 0.35 years v. 13.8 +/- 0.48 kg/m2 and 2 +/- 0.25 years, respectively). The basal GH concentrations in CRF patients (4.1 +/- 0.8 micrograms/l) were significantly higher than those for the NVSS group (1.56 +/- 0.2 micrograms/l). The peak GH response to clonidine was significantly lower in children with CRF (8.4 +/- 1.7 micrograms/l) v. (19.6 +/- 2.3 micrograms/l) for the control group (P < 0.01). Eight out of the 14 children with CRF did not mount a proper GH response (> 10 micrograms/l) to clonidine stimulation whereas the GH response of all the children with NVSS was above 10 micrograms/l. IGF-I concentrations were higher in patients with CRF (35.6 +/- 10.9 IU/l) compared to those for the NVSS group (22.1 +/- 4.9 IU/l). However, the difference was not statistically significant. There was no significant difference in the FT4, TSH as well as basal (8-h) and ACTH-stimulated cortisol concentrations between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Defective pancreatic alpha and beta cell secretion in thyrotoxicosis.

Pancreatic alpha and beta cell hormone secretion was studied in 11 patients with thyrotoxicosis before and in 7 patients after thyroid function was normalized with either prophylthiouracil or methimazole and propranolol (R). All had IV arginine and IV glucose infusions. Forty control subjects had IV arginine; 21 had IV glucose tests. After arginine, untreated patient had blunted serum insulin at both 15 and 30 minutes (p less than 0.05, p less than 0.001) compared to control subjects, blunted glucagon at 30 minutes (p less than 0.05) and blunted glucose at both 15 and 30 minutes (p less than 0.001, p less than 0.01) compared to control subjects. After glucose, untreated patients had lower nadir glucagon than in the studies with both arginine and glucose infusions. These data document blunted glucagon, suppressed glucose and insulin peaks after arginine in thyrotoxicosis, indicate that both alpha and beta cell hormone secretion may be abnormal, and that the preferential abnormality follows protein rather than carbohydrate loading.

Adolescent↗
PubMed1987

Recumbent cranial diabetes insipidus. Studies in a patient with adipsia, hypernatremia, poikilothermia and polyphagia.

A male, aged 16, with chronic hypernatremia, adipsia, polyphagia, and poikilothermia was studied regarding regulation and secretion of arginine vasopressin. During recumbency at night, low plasma arginine vasopressin levels and increased volumes of dilute urine were found; whereas plasma arginine vasopressin levels and urine osmolalities rose and urine volumes decreased during ambulation in the daytime. Neither a 25% reduction of mean arterial pressure nor hypertonic saline infusion increased plasma arginine vasopressin or urine osmolalities. Treatment with 1-desamino-D-arginine-vasopressin at 6 p.m. and a scheduled fluid intake according to actual body weight eradicated hypernatremia and hyperosmolality. These data demonstrate a complete loss of arginine vasopressin secretion to osmotic stimulation, a partial defect of arginine vasopressin secretion to non-osmotic stimulation, an abolished response to stimulation of high-pressure-baroreceptors, but an intact responsiveness to stimulation of low-pressure-baroreceptors.

Adolescent↗
PubMed1998

The cytochrome c maturation operon is involved in manganese oxidation in Pseudomonas putida GB-1.

A Pseudomonas putida strain, strain GB-1, oxidizes Mn2+ to Mn oxide in the early stationary growth phase. It also secretes a siderophore (identified as pyoverdine) when it is subjected to iron limitation. After transposon (Tn5) mutagenesis several classes of mutants with differences in Mn2+ oxidation and/or secretion of the Mn2+-oxidizing activity were identified. Preliminary analysis of the Tn5 insertion site in one of the nonoxidizing mutants suggested that a multicopper oxidase-related enzyme is involved in Mn2+ oxidation. The insertion site in another mutant was preliminarily identified as a gene involved in the general protein secretion pathway. Two mutants defective in Mn2+-oxidizing activity also secreted porphyrins into the medium and appeared to be derepressed for pyoverdine production. These strains were chosen for detailed analysis. Both mutants were shown to contain Tn5 insertions in the ccmF gene, which is part of the cytochrome c maturation operon. They were cytochrome oxidase negative and did not contain c-type cytochromes. Complementation with part of the ccm operon isolated from the wild type restored the phenotype of the parent strain. These results indicate that a functional ccm operon is required for Mn2+ oxidation in P. putida GB-1. A possible relationship between porphyrin secretion resulting from the ccm mutation and stimulation of pyoverdine production is discussed.

Amino Acid Sequence↗
PubMed2001

CFTR: interacting with everything?

More than 1,300 different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) are the cause for cystic fibrosis. CFTR is in charge of proper secretion and absorption of electrolytes, and thus the disease is characterized by defective epithelial Cl(-) secretion and enhanced Na(+) absorption. Recent studies show that CFTR interacts with other proteins via PDZ domains.

Absorption↗
PubMed2004

Beta-cell dysfunction in classic transient neonatal diabetes is characterized by impaired insulin response to glucose but normal response to glucagon.

OBJECTIVE: To investigate beta-cell function and the long-term health of four case subjects presenting with chromosome 6-associated transient neonatal diabetes (TND). RESEARCH DESIGN AND METHODS: Two unrelated case subjects presenting with paternal uniparental isodisomy of chromosome 6 (UPD6) and two siblings with a paternally inherited duplication of 6q24 were studied. Three case subjects presented with neonatal diabetes that recurred at 4-17 years, while diabetes was incidentally discovered in the other case subject at 14 years of age. beta-Cell function was investigated after diabetes relapse by means of an oral glucose tolerance test (OGTT), an intravenous glucose tolerance test (IVGTT), and glucagon tests. The quantitative insulin sensitivity check index (QUICKI) was calculated from fasting blood samples as an estimate of insulin sensitivity. RESULTS: beta-Cell function was investigated at diabetes relapse in two case subjects: the insulin response to both an OGTT and IVGTT was low, whereas the basal levels of C-peptide were normal. No evidence of insulin resistance was found. Residual beta-cell function was further explored by a glucagon test in all subjects at the age of 16-28 years and was found to be normal. Final height was within the normal percentiles, whereas one case, who had been poorly controlled since puberty, presented with diabetes-related microvascular complications. CONCLUSIONS: In patients with chromosome 6-associated TND, the beta-cell is preserved and able to secrete insulin through the stimulatory G protein pathway while exhibiting a specific defect of insulin secretion after glucose stimulation. This form of diabetes can be managed with insulin or diet, although new therapeutic agents (glucagon-like synthetic analogs) may prove useful in the future. Lack of treatment leads to long-lasting hyperglycemia without the risk of ketoacidosis but associated with microangiopathy in adult life.

Chromosome Aberrations↗
PubMed2000

Two novel type 2N von Willebrand disease-causing mutations that result in defective factor VIII binding, multimerization, and secretion of von Willebrand factor.

Two novel mutations, a T-to-C transition at nucleotide 2612 and a T-to-G transversion at nucleotide 3923 of the von Willebrand factor (vWF) complementary DNA, were detected by analysis of the vWF gene in DNA from members of 2 families with atypical von Willebrand disease. The T2612C transition predicts substitution of cysteine by arginine at amino acid position 788 (C788R), and the T3923G transversion predicts substitution of cysteine by glycine at position 1225 (C1225G) of pre-pro-vWF. The patients homozygous for the C788R and C1225G mutations both had a partial vWF deficiency (0. 18 IU/mL and 0.07 IU/mL vWF antigen, respectively); vWF in plasma from patients homozygous for either the C788R or the C1225G mutation failed to bind factor VIII and lacked high molecular weight multimers. Recombinant (r) vWF molecules having the C788R or C1225G mutation were expressed in COS-7 cells. Both rvWF C788R and rvWF C1225G exhibited significantly impaired secretion and failed to bind factor VIII. Recombinant vWF C788R in COS-7 culture medium showed a severe reduction in high molecular weight multimers, whereas rvWF C1225G showed a very mild reduction in high molecular weight multimers when compared with wild-type rvWF. (Blood. 2000;95:2000-2007)

Animals↗
PubMed1988

The phenotype of five classes of T lymphoma mutants. Defective glycophospholipid anchoring, rapid degradation, and secretion of Thy-1 glycoprotein.

Thy-1 glycoprotein is a member of a class of proteins which are anchored to the plasma membrane via a covalently bound glycophospholipid. The biosynthesis and anchoring of Thy-1 were investigated in a family of wild-type and mutant (complementation groups A, B, C, E, and F) T lymphomas. The mutants all synthesize Thy-1 but fail to express it on the cell surface. Analysis of the size of D-[2-3H]mannose-labeled dolichol-linked oligosaccharides showed that the class E mutant is the only cell line which does not synthesize dolichol-P-P-Glc3Man9GlcNAc2. Turnover and possible secretion of Thy-1 by mutant T lymphoma cells were documented in D-[2-3H]mannose pulse-chase experiments. The turnover of [3H]Thy-1 for all wild-type cells is considerably slower than for the mutant cells. Class B and E cells release appreciably more [3H]Thy-1 than wild-type cells. Additional experiments were performed to determine the electrophoretic mobility and hydrophobicity of cell-associated and released forms of Thy-1 labeled overnight with [3H]mannose. All wild-type and class A, C, E, and F mutant cells contain a major Triton X-114 binding species of cell-associated [3H]Thy-1. All extracellular [3H]Thy-1 was almost exclusively hydrophilic. The presence of two Thy-1 anchor components, ethanolamine and palmitate, was investigated. Biosynthetic labeling with [3H]palmitic acid showed that all of the wild-type cells but none of the mutants incorporated this anchor precursor into Thy-1. In [3H]ethanolamine-labeling experiments, incorporation was detected in the Thy-1 of all wild-type cells and in two mutants, S1A-b and T1M1-c. Based on the above studies, the phenotype of Thy-1 negative T lymphoma mutants can be re-evaluated. In classes A and F, dolichol-linked oligosaccharides appear normal and no anchor is detected. In class B, dolichol-linked oligosaccharides appear normal, a partial anchor may be present, and a substantial amount of Thy-1 is released. In class C, dolichol-linked oligosaccharides appear normal and a partial anchor may be present. In class E, truncated dolichol-linked oligosaccharides are formed, no anchor is detected, but a substantial amount of newly synthesized Thy-1 is released. These observations are discussed with reference to the possibility that the lesions which characterize the mutants pertain to the biosynthesis of the glycophospholipid moiety of Thy-1.

Animals↗