PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 9700469

High plasma free fatty acids decrease splanchnic glucose uptake in patients with non-insulin-dependent diabetes mellitus.

T Tomita·Y Yamasaki·M Kubota·R Tohdo·M Katsura·M Ikeda·I Nakahara·Y Shiba·M Matsuhisa·M Hori
View original source ↗Export metadata ↓

Abstract

It has been proposed that high plasma free fatty acid (FFA) levels observed in patients with non-insulin dependent diabetes mellitus (NIDDM) contribute to the development of their insulin resistance. We examined patients with NIDDM to find whether maintaining plasma FFA levels in the fasting range with a euglycemic hyperinsulinemic clamp combined with an oral glucose load (clamp OGL) would affect insulin-mediated peripheral glucose uptake (PGU) and splanchnic glucose uptake (SGU). Nine NIDDM subjects (age, 55 +/- 3 years; duration of diabetes, 11 +/- 2 years; body mass index, 21.0 +/- 0.4 kg/m2; hemoglobin A1c, 9.0 +/- 0.3%; fasting plasma glucose, 9.4 +/- 3.0 mmol/l, means +/- SEM) were hospitalized and treated with diet, oral hypoglycemic agents or insulin for at least 2 weeks to maintain fasting plasma glucose < 8 mmol/l. All the patients were subjected to two different protocols in a random order. On one protocol, under the hyperinsulinemic condition, FFAs were maintained at the their fasting levels (1.19 +/- 0.08) by triglyceride emulsion infusion (Lipid infusion study, L), and on the other protocol, FFAs were made to fall (0.26 +/- 0.06 mmol/l) with saline instead of triglyceride emulsion infusion (Saline infusion study, S). During euglycemic (L, 5.4 +/- 0.2; S, 5.1 +/- 0.2 mmol/l) hyperinsulinemic (L, 1377 +/- 108; S, 1328 +/- 67 pmol/l) clamp, high FFA levels significantly reduced PGU (L, 26.7 +/- 3.6; S, 32.1 +/- 3.4 mumol.kg-1.min-1, P < 0.05) and SGU (L, 12.1 +/- 4.2; S, 27.5 +/- 5.6%, P < 0.05). In conclusion, high FFA levels in patients with NIDDM impaired insulin-mediated glucose uptake in the splanchnic as well as peripheral tissues.

Explore related subjects

3-Hydroxybutyric AcidBlood GlucoseC-PeptideDiabetes Mellitus, Type 2FastingFat Emulsions, IntravenousFatty Acids, NonesterifiedFemaleGlucose Clamp TechniqueHumansHydroxybutyratesInsulinMaleMiddle AgedSplanchnic CirculationTriglyceridesClinical TrialJournal ArticleRandomized Controlled Trial

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

T Tomita, Y Yamasaki, M Kubota, R Tohdo, M Katsura, M Ikeda, I Nakahara, Y Shiba, M Matsuhisa, M Hori. 1998. High plasma free fatty acids decrease splanchnic glucose uptake in patients with non-insulin-dependent diabetes mellitus.. https://doi.org/10.1507/endocrj.45.165

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed1999

Nonapeptide analogues containing (R)-3-hydroxybutanoate and beta-homoalanine oligomers: synthesis and binding affinity to a class I major histocompatibility complex protein.

Crystal structures of antigenic peptides bound to class I MHC proteins suggest that chemical modifications of the central part of the bound peptide should not alter binding affinity to the MHC restriction protein but could perturb the T-cell response to the parent epitope. In our effort in designing nonpeptidic high-affinity ligands for class I MHC proteins, oligomers of (R)-3-hydroxybutanoate and(or) beta-homoalanine have been substituted for the central part of a HLA-B27-restricted T-cell epitope of viral origin. The affinity of six modified peptides to the B2705 allele was determined by an in vitro stabilization assay. Four out of the six designed analogues presented an affinity similar to that of the parent peptide. Two compounds, sharing the same stereochemistry (R,R,S,S) at the four stereogenic centers of the nonpeptidic spacer, bound to B2705 with a 5-6-fold decreased affinity. Although the chiral spacers do not strongly interact with the protein active site, there are configurations which are not accepted by the MHC binding groove, probably because of improper orientation of some lateral substituents in the bound state and different conformational behavior in the free state. However we demonstrate that beta-amino acids can be incorporated in the sequence of viral T-cell epitopes without impairing MHC binding. The presented structure-activity relationships open the door to the rational design of peptide-based vaccines and of nonnatural T-cell receptor antagonists aimed at blocking peptide-specific T-cell responses in MHC-associated autoimmune diseases.

3-Hydroxybutyric Acid↗
PubMed1999

Prevalence of ketonemia and associations with herd size, lactation stage, parity, and postparturient diseases in Jordanian dairy cattle.

The prevalence of bovine ketonemia among 1155 dairy cows in various stages of lactation and parity on 25 Jordanian dairy herds was studied. The cross-sectional study was conducted during the spring of 1992. Serum concentration of beta-hydroxybutyrate (BHB) <0.9 mmol/l, between 0.9 and 1.7 mmol/l, and >1.7 mmol/l were considered to indicate normal, mild and severe ketonemia, respectively. The point prevalences of mild and severe ketonemia were 22% and 3.8%, respectively. The prevalence of ketonemia decreased with increasing herd size. Associations between the prevalence of ketonemia and parity, stage of lactation, metritis, somatic-cell count (SCC) and serum cholesterol levels were not significant (p > 0.05).

3-Hydroxybutyric Acid↗
PubMed1999

Hepatic lipidosis in llamas and alpacas: 31 cases (1991-1997).

OBJECTIVE: To identify factors associated with hepatic lipidosis (HL) in llamas and alpacas. DESIGN: Retrospective case series. ANIMALS: 30 llamas and 1 alpaca. PROCEDURES: Medical records were searched to identify llamas or alpacas in which a histologic diagnosis of HL was made. Information was retrieved on signalment, history, clinical and laboratory findings, and results of necropsy or examination of biopsy specimens. Data were analyzed using descriptive statistics and chi 2 analyses. RESULTS: Females were affected more often than males; however, the sex distribution was not different from that of the camelid population in the diagnostic laboratory's database. Fifty-four percent of the females were pregnant, and 46% were lactating. Most affected camelids were 6 to 10 years old. Anorexia and recent weight loss were common (51.6% of camelids). An infective agent was found in only one ilama, and toxins and mineral deficiencies were not identified. The most common abnormalities on serum biochemical analysis were a high concentration of bile acids, high activities of gamma-glutamyltransferase (GGT) and aspartate aminotransferase (AST), and hypoproteinemia. Concentrations of nonesterified fatty acids (NEFA) and beta-hydroxybutyrate (beta-HB) were high in those camelids in which these compounds were assayed. Twenty-nine camelids did not survive. CLINICAL IMPLICATIONS: Sick camelids should be considered at risk for developing HL, especially those with anorexia or the metabolic demands of pregnancy and lactation. Other stresses also appear to contribute. High concentrations of NEFA, beta-HB, and bile acids; high activities of GGT and AST; and hypoproteinemia may indicate that HL has developed.

3-Hydroxybutyric Acid↗