Sugar transport in the small intestine of obese hyperglycemic, fed and fasted mice

Abstract

1. The in vitro transport of 3-0-methyl-D-glucose was measured in the small intestine of obses-hyperglycemic (ob/ob) mice and their lean littermates, fed or fasted for 48 hrs. 2. Transport was much increased in the jejunum of obese animals and, to a lesser extent, in obese mice on a chronic restricted diet. 3. Kinetic studies indicate that the Vmax of transport was significantly greater in obese than in lean mice, whether fed or fasting. Fasting increase the Vmax in lean but not in obese animals. These changes were more prominent in the jejunum. The apparent Km of transport was the same in all four groups. 4. These findings are discussed in relation to the increase in intestinal absorptive functions in diabetes and in some conditions of food restriction or starvation. The results are consistent with the hypothesis that the effects of diabetes and of starvation on intestinal sugar transport reflect an alteration in the same controlling factor.

MONOSACCHARIDE TRANSPORT BY THE SMALL INTESTINE OF LEAN AND GENETICALLY OBESE (ob/ob) MICE

“…von Grimmel et al (1970) also found no effect of genotype on the influx of a single concentration of galactose (55 mM) across the brush border, and in the severely hyperglycaemic (db/db) mouse the kinetics of monosaccharide influx, expressed per millilitre of tissue water are similar to lean controls (Ramaswamy et al 1979). By contrast, Bihler & Freund (1975) found Vmax expressed per millilitre of tissue water substantially elevated in 8-to 12-week-old obese mice compared with lean controls. However, the present work differs from that of Bihler & Freund (1975) in the use of rapid shaking of the medium to minimize the effects of the unstirred water layer (Lherminier & Alvarado, 1981), and in the use of substantially shorter incubation times to obtain an approximation of the initial rate of monosaccharide uptake, and these differences may be the cause of the discrepancy.…”

“…By contrast, Bihler & Freund (1975) found Vmax expressed per millilitre of tissue water substantially elevated in 8-to 12-week-old obese mice compared with lean controls. However, the present work differs from that of Bihler & Freund (1975) in the use of rapid shaking of the medium to minimize the effects of the unstirred water layer (Lherminier & Alvarado, 1981), and in the use of substantially shorter incubation times to obtain an approximation of the initial rate of monosaccharide uptake, and these differences may be the cause of the discrepancy. Despite no effect of the (ob/ob) genotype on transport per gram dry weight there is evidence to support an increase in the total capacity for intestinal monosaccharide transport in obese compared with lean mice by virtue of an enlarged intestine.…”

“…The aim of this work was to establish the nature of the adaptation of monosaccharide transport and to determine whether transport of monosaccharides exhibited a pattern of adaptation similar to that shown by the size of the intestine. Previous measurements of monosaccharide transport by the obese mouse intestine (Binder, Herskovic, Spiro & Spencer, 1966;von Grimmel, Rakow, Rommel, Lacher & Burkhardt, 1970;Bihler & Freund, 1975) did not examine the effect of the development of the syndrome on monosaccharide transport and produced differing conclusions as to the nature of the adaptation.…”

Modulation of gastrointestinal vagal neurocircuits by hyperglycemia

“…Glucose sensing within enteroendocrine cells is also disrupted in diabetes (Lee et al, 2012) as are both the basal expression and function of intestinal sodium-glucose transporters (Bihler and Freund, 1975; Morton and Hanson, 1984; Dyer et al, 2002; Bhutta et al, 2013) suggesting that the increased absorption of glucose further amplifies the disrupted and dysregulated responses of GI neurocircuits to glucose. It is hardly surprising, therefore, that altered vagal sensory and motor fiber functions have been reported in both humans (Tougas et al, 1992) and rodent models of diabetes (Yagihashi and Sima, 1986; Lee et al, 2001, 2012; Regalia et al, 2002).…”

Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport

“…SGLT1 is overexpressed three-to fourfold in patients and animal models of T2DM (8,(13)(14)(15). Other studies have highlighted the importance of SGLT1 in overall glucose homeostasis and weight control: overexpression is associated with profound obesity in murine models (26), whereas intestinal glucose transport is increased in obese animals (5,17,25). We have recently shown that exposure of the proximal intestine to a glucose load leads to a rapid increase in intestinal SGLT1 expression (38) and hypothesized that isolation of this region following RYGB leads to downregulation of intestinal glucose transport.…”