quote:

"What was really astounding to us, however, was that when we fed normal
mice a high-fat diet, we saw this same mechanism of pathogenesis with
attenuation of GnT-4a enzyme levels, reduced Glut-2 glycosylation, and
loss of cell surface Glut-2 expression," said Marth. "This finding may
explain the loss of Glut-2 commonly observed in type 2 diabetes. For
example, transcriptional control of GnT-4a expression may underlie the
pathogenesis of type 2 diabetes in human mature onset diabetes of the
young (MODY), and perhaps in response to leptin signaling deficiency in
db mice."

To explore such possible clinical applications, Marth and his
colleagues are now testing whether over-expression of the GnT-4a gene
in transgenic mice makes them resistant to diabetes induced by a
high-fat diet or by transcriptional factor mutations that cause MODY.

"If our findings can be applied to humans, they should give us
important insights into how type 2 diabetes may be prevented and
treated," he said

unquote

IF their findings can be applied to humans, they might have someting.
Somehow I doubt it.

TC

The study

Lavigne C, Tremblay F, Asselin G, Jacques H, Marette A.    
Prevention of skeletal muscle insulin resistance by dietary cod
protein in high fat-fed rats.
Am J Physiol Endocrinol Metab. 2001 Jul;281(1):E62-71.
PMID: 11404223 [PubMed - indexed for MEDLINE]
<http://ajpendo.physiology.org/cgi/content/full/281/1/E62>

suggests that fish protein may prevent high fat diet induced insulin
resistance and hence type 2 diabetes. Selected citations:

   "In the present study, we tested the hypothesis that fish
   protein may represent a key constituent of fish with
   glucoregulatory activity. Three groups of rats were fed a high-
   fat diet in which the protein source was casein, fish (cod)
   protein, or soy protein; these groups were compared with a
   group of chow-fed controls. High-fat feeding led to severe
   whole body and skeletal muscle insulin resistance in casein- or
   soy protein-fed rats, as assessed by the euglycemic clamp
   technique coupled with measurements of 2-deoxy-D-[(3)H]glucose
   uptake rates by individual tissues. However, feeding cod
   protein fully prevented the development of insulin resistance
   in high fat-fed rats. These animals exhibited higher rates of
   insulin-mediated muscle glucose disposal that were comparable
   to those of chow-fed rats. The beneficial effects of cod
   protein occurred without any reductions in body weight gain,
   adipose tissue accretion, or expression of tumor necrosis
   factor-alpha in fat and muscle. Moreover, L6 myocytes exposed
   to cod protein-derived amino acids showed greater rates of
   insulin-stimulated glucose uptake compared with cells incubated
   with casein- or soy protein-derived amino acids. These data
   demonstrate that feeding cod protein prevents obesity-induced
   muscle insulin resistance in high fat-fed obese rats at least
   in part through a direct action of amino acids on insulin-
   stimulated glucose uptake in skeletal muscle cells.
   
   [...]
   
   INTEREST IN THE ROLE OF FISH and its constituents on glucose
   metabolism arose from the lower incidence of non-insulin-
   dependent diabetes mellitus (NIDDM) in populations consuming
   large amounts of fish (21). These effects have been primarily
   attributed to the presence of fish oil, because omega-3 fatty
   acids have been shown to improve insulin sensitivity in
   insulin-resistant animals (28, 39). However, the beneficial
   effects of omega-3 fatty acids on glucose tolerance in humans
   are still under debate (see Refs. 10 and 24 for reviews).
   Moreover, epidemiological studies suggest that another
   constituent in fish could protect against the development of
   impaired glucose tolerance and NIDDM in lean fish eaters (9).
   
   Few studies have directly addressed the role of dietary
   proteins in the regulation of insulin sensitivity and glucose
   homeostasis. Hubbard and Sanchez (17) reported that a soy
   protein meal induced lower postprandial blood insulin
   concentrations in human subjects than a casein meal. Animal
   studies further showed that rats fed soy protein had lower
   plasma insulin concentrations than those fed casein (43). In
   untreated type 2 diabetic subjects, the insulin response curve
   was lower after ingestion of a meal containing fish or soy
   proteins compared with casein (11). We showed similarly, in
   rats fed a high-sucrose diet, that both cod and soy proteins
   reduced fasting plasma glucose concentrations compared with
   casein. Dietary cod and soy proteins were found to improve
   glucose tolerance and whole body insulin action on glucose
   disposal (22). However, it has been shown that a high-sucrose
   diet induces major impairment of insulin action in the liver,
   with a smaller contribution from peripheral tissues (40). It
   was, therefore, of significant interest to further evaluate the
   effects of those dietary proteins on insulin sensitivity and
   glucose utilization in another model of insulin resistance with
   a more severe defect in insulin-mediated peripheral glucose
   disposal.
   
   The high-fat/sucrose-fed rat is a well established animal model
   of insulin resistance, reproducing the common form of the
   abdominal (visceral)-obese insulin-resistant syndrome seen in
   humans (4, 20, 37, 38). Rats fed this diet rapidly develop
   whole body and marked skeletal muscle insulin resistance (13,
   42). Thus, in the present study, we tested the effect of
   casein, cod protein, and soy protein on whole body insulin
   action and glucose uptake in peripheral tissues of high
   fat-/sucrose-fed rats. The effects of dietary proteins on basal
   and insulin-stimulated glucose uptake in individual tissues was
   investigated by measuring the uptake of 2-deoxy-D-[3H]glucose
   in skeletal muscles, heart, and adipose tissues in vivo.
   Furthermore, we explored the possibility that dietary proteins
   modulate insulin sensitivity by a direct action of protein-
   derived amino acids on skeletal muscle cells.

   [...]

   Cod protein may exert its beneficial effect on insulin
   sensitivity by a direct action of cod protein-derived amino
   acids on insulin-stimulated glucose uptake in skeletal muscle
   cells. To test this possibility, we exposed cultured L6
   myocytes to amino acid (AA) mixtures corresponding to the
   concentrations of plasma amino acids in rats fed chow, casein,
   cod protein, or soy protein diets. Compared with AA mixtures
   corresponding to rats fed casein or soy protein, muscle cells
   exposed to the cod-derived AA mixture showed increased insulin
   action on glucose uptake (Fig. 5). The increasing effect of cod
   protein-derived AA was observed at all doses of insulin tested
   and were statistically significant at 10 and 50 nM vs. soy
   protein-derived AA and at 10 and 500 nM vs. casein-derived AA.

   [...]

   The present study shows that the consumption of cod protein
   (but not casein or soy protein) fully prevented the development
   of skeletal muscle insulin resistance in diet-induced obesity.
   Indeed, in contrast to obese rats consuming either casein or
   soy protein, cod protein-fed obese rats exhibited higher
   insulin-mediated whole body glucose disposal rates that were
   comparable to the rate of nonobese chow-fed rats.

  [...]

   The present study shows that the consumption of cod protein
   (but not casein or soy protein) fully prevented the development
   of skeletal muscle insulin resistance in diet-induced obesity.
   Indeed, in contrast to obese rats consuming either casein or
   soy protein, cod protein-fed obese rats exhibited higher
   insulin-mediated whole body glucose disposal rates that were
   comparable to the rate of nonobese chow-fed rats. It is well
   established that skeletal muscle is a major site of insulin
   resistance when rats are fed a high-fat/sucrose diet (42).

   [...]
   
   It has been reported previously that n-3 fatty acids derived
   from fish oil improve insulin sensitivity in insulin-resistant
   obese rats (27, 38, 39). However, it is very unlikely that the
   preventive effect of cod protein on insulin resistance could be
   attributed to the trace amounts of n-3 fatty acids found in the
   purified cod protein isolate. Indeed, we measured the amounts
   of n-3 fatty acids in our cod protein diet, and they are 150
   times lower than the lowest dietary n-3 fatty acid levels that
   have been shown to improve insulin sensitivity in rats (6% of
   total calories) (38). Moreover, our finding that the cod
   protein-derived amino acid mixture increased insulin-stimulated
   glucose uptake in cultured L6 myocytes indicates that the
   beneficial effect of dietary cod protein on insulin sensitivity
   is mediated mainly by a direct action of cod protein-derived
   amino acids on the myocyte insulin-regulated glucose transport
   system and not by the trace amounts of n-3-fatty acids present
   in the cod protein diet.

   [...]

   The beneficial effect of dietary cod protein on skeletal muscle
   insulin sensitivity was observed even in the face of similar
   body weight gain and visceral adipose tissue accretion compared
   with casein- or soy protein-fed rats. These results strongly
   suggest that dietary cod protein prevented the causal link
   between visceral obesity and the development of peripheral
   insulin resistance.

   [...]

   In summary, the present study shows that dietary cod protein
   prevents the development of skeletal muscle insulin resistance
   in high fat-fed obese rats. The beneficial action of cod
   protein on insulin sensitivity occurred without reductions in
   body weight or adiposity, strongly suggesting that cod protein
   protects from obesity-induced insulin resistance. The effect of
   dietary cod protein appears to involve, at least in part, a
   direct action of cod protein-derived amino acids on insulin-
   stimulated glucose transport in skeletal muscle cells. Interest
   in the present data also arises from the fact that increased
   cod protein consumption is easily implementable in humans
   within guidelines of daily recommended allowances of essential
   nutrients (12, 18) and thus could represent a novel
   nutraceutical approach in preventing the development of insulin
   resistance in obesity. Because insulin resistance is a central
   factor in visceral obesity-associated complications such as
   hypertension, diabetes, and cardiovascular diseases (2, 6, 8),
   dietary cod protein may contribute to prevent the many
   metabolic aberrations that accompany the obese state."

Interestingly in the study

Kim JY, Nolte LA, Hansen PA, Han DH, Ferguson K, Thompson PA, Holloszy
JO.
High-fat diet-induced muscle insulin resistance: relationship to
visceral fat mass.
Am J Physiol Regul Integr Comp Physiol. 2000 Dec;279(6):R2057-65.
PMID: 11080069 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra
ctPlus&list_uids=11080069>

restricting intake of the high-fat diet to 75% of ad libitum
completely prevented the increase in visceral fat and muscle insulin
resistance.

Abstract:

   "It has been variously hypothesized that the insulin resistance
   induced in rodents by a high-fat diet is due to increased
   visceral fat accumulation, to an increase in muscle
   triglyceride (TG) content, or to an effect of diet composition.
   In this study we used a number of interventions: fish oil,
   leptin, caloric restriction, and shorter duration of fat
   feeding, to try to disassociate an increase in visceral fat
   from muscle insulin resistance. Substituting fish oil (18% of
   calories) for corn oil in the high-fat diet partially protected
   against both the increase in visceral fat and muscle insulin
   resistance without affecting muscle TG content. Injections of
   leptin during the last 4 days of a 4-wk period on the high-fat
   diet partially reversed the increase in visceral fat and the
   muscle insulin resistance, while completely normalizing muscle
   TG. Restricting intake of the high-fat diet to 75% of ad
   libitum completely prevented the increase in visceral fat and
   muscle insulin resistance. Maximally insulin-stimulated glucose
   transport was negatively correlated with visceral fat mass (P <
   0.001) in both the soleus and epitrochlearis muscles and with
   muscle TG concentration in the soleus (P < 0.05) but not in the
   epitrochlearis. Thus we were unable to dissociate the increase
   in visceral fat from muscle insulin resistance using a variety
   of approaches. These results support the hypothesis that an
   increase in visceral fat is associated with development of
   muscle insulin resistance."

Let's see what epidemiologial studies say about dietary fat, type 2
diabetes and obesity:

van Dam RM, Willett WC, Rimm EB, Stampfer MJ, Hu FB.
Dietary fat and meat intake in relation to risk of type 2 diabetes in
men.
Diabetes Care. 2002 Mar;25(3):417-24.
PMID: 11874924 [PubMed - indexed for MEDLINE]
<http://care.diabetesjournals.org/cgi/content/full/25/3/417>

   "... CONCLUSIONS: Total and saturated fat intake were
   associated with a higher risk of type 2 diabetes, but these
   associations were not independent of BMI. Frequent consumption
   of processed meats may increase risk of type 2 diabetes."

Salmeron J, Hu FB, Manson JE, Stampfer MJ, Colditz GA, Rimm EB,
Willett WC.
Dietary fat intake and risk of type 2 diabetes in women.
Am J Clin Nutr. 2001 Jun;73(6):1019-26.
PMID: 11382654 [PubMed - indexed for MEDLINE]
<http://www.ajcn.org/cgi/content/full/73/6/1019>

   "... CONCLUSIONS: These data suggest that total fat and
   saturated and monounsaturated fatty acid intakes are not
   associated with risk of type 2 diabetes in women, but that
   trans fatty acids increase and polyunsaturated fatty acids
   reduce risk. Substituting nonhydrogenated polyunsaturated fatty
   acids for trans fatty acids would likely reduce the risk of
   type 2 diabetes substantially."

Willett WC, Leibel RL.
Dietary fat is not a major determinant of body fat.
Am J Med. 2002 Dec 30;113 Suppl 9B:47S-59S. Review.
PMID: 12566139 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra
ctPlus&list_uids=12566139>

Willett WC.
Dietary fat plays a major role in obesity: no.
Obes Rev. 2002 May;3(2):59-68. Review.
PMID: 12120421 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra
ctPlus&list_uids=12120421>